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Metalenses are typically designed for a fixed focal length, restricting their functionality to static scenarios. Various methods have been introduced to achieve the zoom function in metalenses. These methods, however, have a very limited zoom range, or they require additional lenses to achieve direct imaging. Here, we demonstrate a zoom metalens based on axial movement that performs both the imaging and the zoom function. The key innovation is the use of a polynomial phase profile that mimics an aspheric lens, which allows an extended depth of focus, enabling a large zoom range. Experimental results show that this focal length variation, combined with the extended depth of focus, translates into an impressive zoom range of 11.9× while maintaining good imaging quality. We see applications for such a zoom metalens in surveillance cameras of drones or microrobots to reduce their weight and volume, thus enabling more flexible application scenarios.
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The escalating incidence of metabolic pathologies such as obesity and diabetes mellitus underscores the imperative for innovative therapeutics targeting lipid metabolism modulation. Within this context, augmenting thermogenic processes in adipose cells emerges as a viable therapeutic approach. Given the limitations of previous ß3-adrenergic receptor (ß3-AR) agonist treatments in human diseases, there is an increasing focus on therapies targeting the ß2-adrenergic receptor (ß2-AR). Olodaterol (OLO) is a potent ß2-AR agonist that is a potential novel pharmacological candidate in this area. Our study explores the role and underlying mechanisms of OLO in enhancing brown adipose thermogenesis, providing robust evidence from in vitro and in vivo studies. OLO demonstrated a dose-dependent enhancement of lipolysis, notably increasing the expression of Uncoupling Protein 1 (UCP1) and raising the rate of oxygen consumption in primary brown adipocytes. This suggests a significant increase in thermogenic potential and energy expenditure. The administration of OLO to murine models noticeably enhanced cold-induced nonshivering thermogenesis. OLO elevated UCP1 expression in the brown adipose tissue of mice. Furthermore, it promoted brown adipocyte thermogenesis by activating the ß2-AR/cAMP/PKA signaling cascades according to RNA sequencing, western blotting, and molecular docking analysis. This investigation underscores the therapeutic potential of OLO for metabolic ailments and sheds light on the intricate molecular dynamics of adipocyte thermogenesis, laying the groundwork for future targeted therapeutic interventions in human metabolic disorders.
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Adipocitos Marrones , Benzoxazinas , Termogénesis , Ratones , Humanos , Animales , Adipocitos Marrones/metabolismo , Simulación del Acoplamiento Molecular , Termogénesis/genética , Tejido Adiposo Pardo/metabolismo , Transducción de Señal , Obesidad/metabolismo , Agonistas Adrenérgicos beta , Receptores Adrenérgicos , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMEN
Non-alcoholic fatty liver disease (NAFLD) stands as the most prevalent hepatic disorder, with bariatric surgery emerging as the most effective intervention for NAFLD remission. Sleeve gastrectomy (SG) has notably ascended as the predominant procedure due to its comparative simplicity and consistent surgical outcomes. Nonetheless, the underlying mechanisms remain unclear. In this study, we probed the therapeutic potential of SG for NAFLD induced by a high-fat diet (HFD) in mice, with a focus on its impact on liver lipid accumulation, macrophage polarization, and the role of the histone methyltransferase Setdb2. SG prompted significant weight loss, diminished liver size and liver-to-body weight ratio, and enhanced liver function, evidenced by reduced serum levels of triglycerides (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination confirmed a reduction in liver lipid accumulation. Additionally, flow cytometry unveiled an increased proportion of M2 macrophages and a decrease in Setdb2 expression was shown in the SG group, suggesting an association between Setdb2 levels and postsurgical macrophage polarization. Furthermore, the conditional knockout of Setdb2 in mice further mitigated HFD-induced steatosis and promoted the M2 macrophage phenotype. Mechanistically, Setdb2 knockout in bone marrow-derived macrophages (BMDMs) favored M2 polarization, with RNA sequencing and western blotting analyses corroborating the upregulation of the PI3K/Akt signaling pathway. The effects of Setdb2 on macrophage activation were nullified by the PI3K inhibitor LY294002, suggesting that Setdb2 facilitates alternative macrophage activation through the PI3K/Akt signaling pathway. These comprehensive findings underscore the potential of SG as a therapeutic intervention for NAFLD by regulating the critical function of Setdb2 in macrophage polarization and activation, thereby offering novel insights into NAFLD pathogenesis and therapeutic targets.
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Regulación hacia Abajo , Gastrectomía , N-Metiltransferasa de Histona-Lisina , Activación de Macrófagos , Macrófagos , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/etiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Macrófagos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Masculino , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/patología , Metabolismo de los LípidosRESUMEN
This study was designed to investigate the roles of autophagy in the attenuation of hepatic lipid accumulation after sleeve gastrectomy (SG). Thirty-two rats were divided into normal control, obesity group, sham group, and SG group. Then serum glucagon-like polypeptide-1 (GLP-1) and lipid accumulation were determined, followed by measuring the activity of autophagy based on immunohistochemistry (IHC) and Western blot analysis. Our data showed significant decrease in the lipid accumulation after SG compared with sham group. GLP-1 and autophagy showed significant increase in rats underwent SG compared with the sham group (P < 0.05). In vitro experiments were conducted to analyze the roles of GLP-1 in autophagy. We knock-downed the expression of Beclin-1 in HepG2, and then analyzed the expression of autophagy-related protein (i.e. LC3BII and LC3BI) and lipid droplet accumulation. In HepG2 cells, GLP-1 analog reduced lipid accumulation by activating autophagy through modulating the AMPK/mTOR signaling pathway. All these concluded that SG decreased hepatic lipid accumulation by inducing autophagy through modulating AMPK/mTOR pathway.
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Proteínas Quinasas Activadas por AMP , Serina-Treonina Quinasas TOR , Animales , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia , Gastrectomía , Péptido 1 Similar al Glucagón/metabolismo , Lípidos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
We present a theoretical study that combines thermal and optomechanical effects to investigate their influences on the formation of the optical frequency comb (OFC) in whispering-gallery-mode (WGM) microcavities. The results show that the cut-off order and center frequency of OFC affected by thermal effects exhibit an overall redshift by varying the power and detuning of the pump field, which provides the possibility of tuning the offset frequency of OFC. Our study demonstrates a method to characterize the effect on the generation of OFC and the tuning of its offset frequency in a WGM resonator with opto-thermo-mechanical properties and pave the way for the future development of OFC in thermo-optomechanical environments.
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BACKGROUND: This study was designed to investigate the feasibility and safety of laparoscopic hepatic caudate lobectomy (LHCL) for treating liver tumor by comparing with the open hepatic caudate lobectomy (OHCL). METHODS: In the LHCL group, we included 24 patients with liver tumor received LHCL in Qilu Hospital of the Shandong University from January 2014 to January 2019. Meanwhile, 24 matched liver tumor patients underwent OHCL in our hospital served as control. Then we compared the patient characteristics, intraoperative parameters, and postoperative outcomes between LHCL group and OHCL group. RESULTS: There were no significant differences in gender, age, degree of cirrhosis, tumor size, preoperative liver function, Child-Pugh grading, proportion of liver cirrhosis, and tumor size between LHCL group and OHCL group (P > 0.05). No death was reported in both groups. The length of incision in LHCL group was significantly lower than that in OHCL group (4.22 ± 1.14 cm vs. 22.46 ± 4.40 cm, P < 0.001). The intraoperative blood loss in LHCL group was significantly lower than that of OHCL group (116.82 ± 71.61 ml vs. 371.74 ± 579.35 ml, P = 0.047). The total operation time, Pringle maneuver occlusion time, and blocking rate in LHCL group showed no statistical difference compared with those of the OHCL group (P > 0.05). The VAS scores at postoperative 24 and 48 h showed no statistical differences between LHCL group and OHCL group (P > 0.05). Compared with the OHCL group, significant decrease was noticed in the proportion of patients with severe pain 48 h after surgery (0 vs. 4.25 ± 0.46, P < 0.001) and dezocine consumption (90.45 ± 45.77 mg vs. 131.6 ± 81.30 mg, P = 0.0448) in the LHCL group. CONCLUSION: LHCL is effective and feasible for treating liver tumor, which is featured by reducing intraoperative blood loss and serious pain.
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Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Humanos , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Hepatectomía , Neoplasias Hepáticas/cirugía , Cirrosis Hepática/cirugía , Carcinoma Hepatocelular/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Whether to preserve the uterine round ligament during laparoscopic inguinal hernia repair in women is controversial. In this study, we aimed to compare outcomes of uterine round ligament preservation versus transection during such surgery and to explore the impact and long-term outcomes of transecting the round ligament. METHODS: The study cohort comprised 419 women who had undergone laparoscopic inguinal hernia repair in Beijing Chaoyang Hospital and Qilu Hospital from January 2013 to January 2020; 393 (93.8%) of whom were successfully followed up. Patient characteristics and technical details of the operative procedure were collected and analyzed retrospectively. Early and late postoperative follow-up data, complications, especially symptoms related to retroflexed uterus, and fertility outcomes, were collected by a single follow-up nurse who was blinded to the operative procedure. RESULTS: There were 218 women (239 sides) in the uterine round ligament preservation group and 175 (182 sides) in the transection group. The patients in the preservation group were younger (45.9 vs. 53.6 years, p = 0.000), and had lower American Society of Anesthesiologists scores (p = 0.000). The median follow-up times in the preservation and transection groups were 41.8 ± 24.2 and 42.7 ± 24.6 months, respectively (p = 0.692). Compared with the transection group, the preservation group had longer operative times for repair of both primary and recurrent hernias. Intraoperative bleeding, length of hospital stay, development of seromas, recurrence rate, incidence of postoperative pain at the first and third postoperative months, and time of last outpatient visit were similar in the two groups. There were more premenopausal patients in the preservation group; however, we found no evidence that transection of the round ligament affected subsequent pregnancy or childbirth. Moreover, we identified no differences in dyspareunia, dysmenorrhea, chronic pelvic pain, or uterine prolapse. CONCLUSION: Transection of the round ligament during laparoscopic inguinal hernia repair in women does not increase the incidence of dyspareunia, dysmenorrhea, chronic pelvic pain, or uterine prolapse, whereas it has the advantage of reducing the operation time.
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Dispareunia , Hernia Inguinal , Laparoscopía , Ligamentos Redondos , Prolapso Uterino , Dismenorrea/cirugía , Femenino , Estudios de Seguimiento , Hernia Inguinal/cirugía , Herniorrafia/métodos , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Masculino , Dolor Pélvico/cirugía , Embarazo , Estudios Retrospectivos , Ligamentos Redondos/cirugía , Prolapso Uterino/cirugíaRESUMEN
The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB), and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied on both groups to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake assessed with the Morris water maze (MWM) and positron emission tomography (PET). Insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptake-related proteins including glucose transporter 1 (GLUT-1), GLUT-4, phospho-Akt substrate of 160kDa (pAS160), AS160, Rab10, Myosin-Va as well as the c-fos marker in the brain were examined. Along with augmented glucose homeostasis following DJB, central GLP-1 was correlated with the improved cognitive function and ameliorated brain glucose uptake, which was further confirmed by the enhancive role of Lira on both groups whereas the Exe-9 and Glp-1r KD were opposite. Known to activate insulin-signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB.NEW & NOTEWORTHY The improvement of cognitive function following bariatric surgery has been highlighted while its mechanisms remain elusive. The brain glucose uptake of patients was improved after RYGB, and the DJB and sham surgery performed on obese and diabetic Wistar rats revealed that the elevated central GLP-1 contributes to the dramatic improvement of cognitive function, brain glucose uptake, transport, glucose sensing, and neuronal activation.
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Cognición , Diabetes Mellitus Experimental/metabolismo , Derivación Gástrica , Péptido 1 Similar al Glucagón/metabolismo , Obesidad/metabolismo , Animales , Encéfalo/metabolismo , Duodeno/cirugía , Glucosa , Yeyuno/cirugía , Obesidad/cirugía , Ratas WistarRESUMEN
Sleeve gastrectomy (SG) is the most widely used bariatric procedures globally, which could improve glucose and lipid metabolism dramatically. Circular RNAs (circRNAs) are being increasingly implicated in numerous pathophysiological processes. However, for diabetes mellitus (DM), the expression and function of circRNAs remain largely undetermined, in particular, whether circRNAs mediate the amelioration of DM observed after SG. Using a diabetic rat model, we subjected liver tissue from SG and sham-operated rats to RNA sequencing. Amongst the 103 differentially regulated circRNAs identified in diabetic rats after SG, we focused on circDOCK7, a highly expressed circRNA derived from the back-splicing of the DOCK7 gene. Silencing of circDOCK7 significantly inhibited cellular proliferation and induction of apoptosis in insulin-resistant rat hepatocytes. Further analysis indicated circDOCK7 harbored binding sites for miR-139-3p and regulated the expression of minichromosome maintenance 3 (MCM3) through sequestration of miR-139-3p. Our findings therefore demonstrate a novel regulatory pathway involving circDOCK7 that regulates cellular proliferation and apoptosis through increasing the expression of MCM3. Overall, our study establishes a list of specific circRNAs expressed in diabetic rat liver after SG including circDOCK7 which serve as potential biomarkers and treatment targets for DM patients.
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Apoptosis/genética , Diabetes Mellitus Experimental/genética , Regulación hacia Abajo/genética , Gastrectomía , Hepatocitos/patología , MicroARNs/metabolismo , Componente 3 del Complejo de Mantenimiento de Minicromosoma/metabolismo , ARN Circular/metabolismo , Animales , Secuencia de Bases , Peso Corporal , Línea Celular , Proliferación Celular/genética , Diabetes Mellitus Experimental/patología , Conducta Alimentaria , Silenciador del Gen , Glucosa/metabolismo , Hepatocitos/metabolismo , Homeostasis , Masculino , MicroARNs/genética , Componente 3 del Complejo de Mantenimiento de Minicromosoma/genética , Estabilidad del ARN/genética , ARN Circular/genética , Ratas WistarRESUMEN
BACKGROUND: Bariatric surgeries have been shown to be effective in reversing damaged pulmonary function in individuals suffering from obesity and type 2 diabetes mellitus, whereas its underlying mechanisms remain largely unknown. METHODS: Sleeve gastrectomy (SG) was performed on obese and diabetic Wistar rats, and their pulmonary function and lung tissues were compared to sham-operated (SH) obese and diabetic rats, and age-matched healthy controls (C) to explore the improvements in microstructures and expression of surfactant protein (SP)-A and -C at postoperative 4th, 8th, and 12th week. RESULT: Apart from the profound metabolic changes and improvement in pulmonary function, lung volume was restored along with an improved diffusion capacity noted by thinned capillary basement membrane and decreased harmonic mean length of diffusion barrier in SG rats. The digital slices of light microscope showed the general changes brought on by the SG, including normalized basic structures, ameliorated inflammatory status, as well as reduced lipid deposition, where the hydroxyproline (HYP), triglyceride (TG) assays, and electron microscope further suggested that the improvement in alveolar structures lies in reduced collagen fibers, lipids and septal tissues, increased capillary blood, and normalized alveolar type 2 (AT2) cells. Besides, disrupted SP-A and SP-C expression were also normalized after SG. CONCLUSION: The improvement of lung function after SG is related to the ameliorated alveolar structures, and surface protein expression induced by weight loss and improved glucose metabolism.
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Diabetes Mellitus Experimental/cirugía , Gastrectomía , Obesidad/cirugía , Alveolos Pulmonares/anatomía & histología , Surfactantes Pulmonares/química , Animales , Pulmón , Alveolos Pulmonares/patología , Alveolos Pulmonares/ultraestructura , Ratas , Ratas Wistar , Pérdida de PesoRESUMEN
Based on silica microsphere resonators embedded with iron oxide nanoparticles, we proposed and fabricated an all-optical and continuously tunable polarization beam splitter (PBS), and a broadband optical power sensor (OPS) with high sensitivity. The PBS is realized since the effective refractive indexes of the transverse-electric and transverse-magnetic polarization modes in the microsphere resonator are different. Due to the excellent photothermal effect of iron oxide nanoparticles, we realized the all-optical and continuously tunable PBS based on the hybrid microsphere resonator. A maximum polarization splitting ratio of 20 dB and a tuning range of 5 nm are achieved. Based on this mechanism, the hybrid microsphere resonator can also be used as a broadband OPS. The sensitivity of the OPS is 0.487 nm/mW, 0.477 nm/mW, and 0.398 nm/mW when the probe wavelength is 690 nm, 980 nm, and 1550 nm, respectively. With such good performances, the tunable PBS and the broadband OPS have great potential in applications such as optical routers, switches and filters.
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Gastric adenocarcinoma is an important death-related cancer. To find factors related to survival and prognosis, and thus improve recovery prospects, a powerful signature is needed. DNA methylation plays an important role in gastric adenocarcinoma processes and development, and here we report on the search for a significant DNA methylation gene to aid with the earlier diagnosis of gastric adenocarcinoma patients. A Cox proportional risk regression analysis and random survival forest algorithm were used to analyze gastric adenocarcinoma patients' DNA methylation data from The Cancer Genome Atlas, a public database. DNA methylation gene signature consisting of five genes (SERPINA3, AP000357.4, GZMA, AC004702.2, and GREB1L) were selected. As the most accurate predictor, the area under the curve in the training and test group were 0.72 and 0.61, respectively. The signature was able to sort patients into high- and low-risk groups with meaningful overall survival rates (median: 18.36 vs 72.23 months, log-rank test, P < 0.001) in the training group, which predictive ability was validated in a test data set (median: 25.56 vs 58.80 months, log-rank test, P < 0.016). A multivariate Cox regression analysis showed the significant DNA methylation was an independent prediction prognostic factor for gastric adenocarcinoma patients. Functional analysis suggests that these signature genes may be related to pathways and biological processes associated with tumorigenesis. The significant DNA methylation gene could be a novel prediction and prognostic biomarker that both aids in the treatment and predicts the overall survival likelihoods of gastric adenocarcinoma patients.
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We demonstrate that discrete solitons are possible in a micro-fabricated optomechanical structure, which consists of N identical cells. Analyses illustrate that these states originate from photon-phonon interaction or optomechanical effect. In principle, the self-localized entities are capable of exhibiting very slow velocities, depending on the photon hopping rate and phase difference among successive optomechanical cells. The theoretical results pave the way for a new type of on-chip system to observe discrete optical solitons behaviors and may have potential application in on-chip manipulation of photonic information processing.
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BACKGROUND: Seroma is the most common early minor complication of inguinal hernia repair. Seromas generally resolve spontaneously within a few weeks, but can sometimes cause other complications. The optimal ways to repair inguinal hernia and handle the hernial sac are still debatable. Large scale, prospective, randomized, controlled studies focusing on the correlation between transection of the hernial sac and seroma formation are scarce. METHODS: A total of 159 adult male patients with primary indirect inguinal hernia who underwent laparoscopic transabdominal preperitoneal repair were recruited. The patients were randomized to undergo either complete dissection or transection of the hernial sacs. Patients were followed up at postoperative 7 days, 1 and 3 months, looking specifically for seroma. Seroma was diagnosed via physical examination, and a prestructured form was used to evaluate patient recovery and define the type of seroma present at each follow-up visit. RESULTS: There were 83 patients in the completely dissected group and 76 in the transected group. The overall incidence of postoperative seroma was 12.6% (n = 20). The χ2 test demonstrated that significantly more patients developed seroma in the transected group than in the completely dissected group (18.4% vs. 7.2%, p = 0.034); there were also significant differences between the two groups in the incidences of seroma at postoperative 7 days (18.4% vs. 6.0%, p = 0.016) and 1 month (14.5% vs. 4.8%, p = 0.037). Seroma formation was correlated with age, body mass index, use of anticoagulants, hernia type, hernia size, sac size, and operative time. There were no significant differences between the two groups in the degree of postoperative pain and time taken for the resumption of outdoor activities. CONCLUSIONS: When using the laparoscopic transabdominal preperitoneal technique for indirect inguinal hernia repair, the risk of postoperative seroma formation is greater after transection compared with complete dissection of the hernial sac.
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Hernia Inguinal/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Seroma/etiología , Adulto , Factores de Edad , Anciano , Anticoagulantes/uso terapéutico , Índice de Masa Corporal , Estudios de Seguimiento , Hernia Inguinal/patología , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Dolor Postoperatorio/etiología , Examen Físico , Complicaciones Posoperatorias , Estudios Prospectivos , Seroma/diagnósticoRESUMEN
Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.
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Cirugía Bariátrica , Ácidos y Sales Biliares , Circulación Enterohepática/fisiología , Obesidad , Complicaciones Posoperatorias/metabolismo , Taurina/metabolismo , Animales , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/clasificación , Cirugía Bariátrica/métodos , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/metabolismo , Glucemia/metabolismo , Peso Corporal/fisiología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Reabsorción Intestinal/fisiología , Obesidad/metabolismo , Obesidad/fisiopatología , Obesidad/cirugía , RatasRESUMEN
Bariatric surgery has been reported to relieve diabetic cardiomyopathy (DCM) effectively. However, the mechanisms remain largely unknown. To determine the effects of bariatric surgery on DCM via modulation of myocardial Ca2+ homeostasis and autophagy, sleeve gastrectomy (SG), duodenal-jejunal bypass (DJB), and sham surgeries were performed in diabetic rats induced by high-fat diet and a low dose of streptozotocin. Cardiac remodeling was assessed by a series of morphometric and histological analyses. Transthoracic echocardiography and hemodynamic measurements were performed to determine cardiac function. Ca2+ homeostasis was evaluated by measuring Ca2+ transients with fura-2 AM in isolated ventricular myocytes along with detection of the abundance of Ca2+ regulatory proteins in the myocardium. Myocardial autophagic flux was determined by expression of autophagy-related proteins in the absence and presence of chloroquine. Both SG and DJB surgery alleviated DCM morphologically and functionally. Ca2+ transients exhibited a significantly higher amplitude and faster decay after SG and DJB, which could be partially explained by increased expression of ryanodine receptor 2, sarco(endo)plasmic reticulum Ca2+-2ATPase, 12.6-kDa FK506-binding protein, and hyperphosphorylation of phospholamban. In addition, a lower level of light chain 3B and higher level of p62 were detected after both SG and DJB, which was not reversed by chloroquine treatment and associated with activated mammalian target of rapamycin and attenuated AMP-activated protein kinase signaling pathway. Collectively, these results provided evidence that bariatric surgery could alleviate DCM effectively, which may result, at least in part, from facilitated Ca2+ homeostasis and attenuated autophagy, suggesting a potential choice for treatment of DCM when properly implemented. NEW & NOTEWORTHY The present study is the first to investigate the modulation of myocardial Ca2+ homeostasis and autophagy after bariatric surgery and to examine its effects on diabetic cardiomyopathy. Bariatric surgery could facilitate myocardial Ca2+ homeostasis and attenuate myocardial autophagy, contributing to the alleviation of cardiomyopathy morphologically and functionally in a diabetic rat model.
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Autofagia , Señalización del Calcio , Cardiomiopatías Diabéticas/prevención & control , Gastrectomía , Derivación Gástrica , Miocardio/metabolismo , Obesidad/cirugía , Animales , Glucemia/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/inducido químicamente , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , Dieta Alta en Grasa , Lípidos/sangre , Masculino , Miocardio/patología , Obesidad/sangre , Obesidad/complicaciones , Ratas Sprague-Dawley , Estreptozocina , Función Ventricular Izquierda , Remodelación Ventricular , Pérdida de PesoRESUMEN
BACKGROUND: There is a high demand for noninvasive screening tools for gastrointestinal cancer (GIC) detection, and GIC-specific markers are required for such purposes. It is established that induction of the telomerase reverse transcriptase gene (TERT) coupled with telomerase activation is essential for cancer development/progression and aberrant TERT promoter methylation of specific 5'-C-phosphate-G-3' (CpGs) has been linked to TERT induction in oncogenesis. Here we analyzed TERT promoter methylation in fecal samples from GIC patients and healthy adults and determined its value as a stool biomarker for GIC detection. MATERIALS AND METHODS: Sixty-nine GIC patients (34 colorectal carcinoma and 35 gastric cancer) and 62 healthy adults were recruited and fecal samples were collected. Paired tumors and adjacent non-cancerous tissues from 34 patients and normal mucosa tissues from 12 healthy individuals were collected. TERT promoter methylation density was determined using pyrosequencing. RESULTS: We identified two GIC-specific methylation sites at -218 (CpG site 1) and -210 (CpG site 2) in the TERT promoter in tumor tissues. Methylated TERT promoter CpG sites 1 and 2 were also detectable in patient stool, while only background levels were observed in healthy individuals. The overall sensitivity reached 52.2% (95% confidence interval [CI]: 48.3-56.0) for fecal methylated TERT promoter assays at 90% specificity, which was comparable to other known stool methylation markers for GIC detection. The combined assays of fecal TERT promoter methylation and occult blood (OB) significantly improved sensitivity and specificity in colorectal cancer (area under curves for methylation alone: 0.798, 95% CI: 0.707-0.889 vs. methylation + OB: 0.920, 95% CI: 0.859-0.981; p = .028), but not in gastric cancer. CONCLUSION: This proof-of-concept study suggests the feasibility of stool TERT promoter methylation analyses as an additional tool in noninvasive GIC screening. IMPLICATIONS FOR PRACTICE: Induction of telomerase reverse transcriptase (TERT) expression coupled with telomerase activation is essential for cancer development/progression, while aberrant TERT promoter methylation has been linked to TERT induction in oncogenesis. We identified two cancer-specific methylation sites (CpG1 and 2) in the TERT promoter in tumors from GIC patients. Methylated TERT promoter CpG sites 1 and 2 were detectable in patient stool, while only background levels were observed in healthy individuals. The sensitivity and specificity was comparable to other known stool methylation markers for GIC detection. This proof-of-concept study suggests the feasibility of stool TERT promoter methylation analyses for noninvasive screening of GIC.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Metilación de ADN , Neoplasias Gástricas/genética , Telomerasa/genética , Secuencia de Aminoácidos , Estudios de Casos y Controles , Neoplasias Colorrectales/enzimología , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , ADN de Neoplasias/metabolismo , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Neoplasias Gástricas/enzimologíaRESUMEN
BACKGROUND: Proper mesh fixation is critical for successful TAPP laparoscopic hernia repair. Conventional mesh fixation may cause chronic neuralgia, groin paresthesia or other complications. This study aimed at introducing a new vacuum suction technique for mesh fixation and evaluating its efficacy and safety compared with traditional staple fixation way. METHODS: Clinical data of 242 patients undergoing TAPP from July 2011 to March 2014 were retrospectively analyzed. Patients were divided into vacuum suction fixation group and staple fixation group. The operation time, hospital stay, complications, recurrence, visual analogue scale pain score and cost were evaluated. RESULTS: All surgeries were successful. The operation time of staple group was (42.34 ± 10.15) min for unilateral hernia and (64.08 ± 16.01) min for bilateral hernias. The postoperative hospital stay was (2.76 ± 0.84) days. One recurrence was observed (0.90%). For vacuum group, the operation time was (42.66 ± 7.76) min and (63.92 ± 10.49) min, and hospital stay was (2.60 ± 0.74) days. No recurrence was observed. There was no significant difference in recurrence, operation time, postoperative pain and hospital stay between two groups (P > 0.05). Average cost were (11,714 ± 726) RMB for vacuum group which was lower than staple group (14,837 ± 1568) RMB (P < 0.05). The top three complications of staple group were scrotal emphysema (10.81%), scrotal seroma (6.31%) and temporary nerve paresthesia (4.50%) while for vacuum group, they were scrotal seroma (3.82%), temporary nerve paresthesia (3.05%), scrotal emphysema (1.53%) and uroschesis (1.53%). The incidence of scrotal emphysema was lower in vacuum group (P < 0.05). No significant difference was observed in other complications (P > 0.05). CONCLUSION: Both techniques for mesh fixation are safe and effective. There is no significant difference in recurrence, operation time, postoperative pain or hospital stay. The vacuum suction fixation technique is more economical with lower incidence of scrotal emphysema.
Asunto(s)
Herniorrafia/métodos , Laparoscopía , Succión , Mallas Quirúrgicas , Engrapadoras Quirúrgicas , Vacio , Femenino , Herniorrafia/economía , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
BACKGROUND: The aim of this randomized controlled study was to determine whether octreotide (OCT) or scopolamine butylbromide (SB) was the more effective antisecretive drug controlling gastrointestinal (GI) symptoms due to malignant bowel obstruction (MBO) caused by advanced ovarian cancer. METHODS: Ninety-seven advanced ovarian cancer patients with inoperable MBO were randomized to OCT 0.3 mg/day (OCT group, n = 48) or SB 60 mg/day (SB group, n = 49) for 3 days through a continuous subcutaneous infusion. The following parameters were measured: episodes of vomiting, nausea, dry mouth, drowsiness, and continuous and colicky pain, using a Likert scale corresponding to a numerical value (none 0, slight 1, moderate 2, severe 3) recorded before starting the treatment (T0) and 24 h (T1), 48 h (T2), and 72 h after (T3) and the daily quantity of GI secretions through the Nasogastric tube (NGT) during the period of study. One patient in the SB group is not included in any assessments since she withdrew consent prior to receiving any treatment because of rapidly progressing cancer. RESULTS: OCT significantly reduced the amount of GI secretions at T1, T2, and T3 (P < 0.05) compared with SB. NGT secretions significantly reduced at T1, T2, and T3 compared with T0 (P < 0.05) in the OCT group, while in the SB group, only at T3, NGT secretions significantly reduced compared with T0. OCT treatment induced a significantly rapid reduction in the number of daily episodes of vomiting and intensity of nausea compared with SB treatment. No significant changes were observed in dry mouth, drowsiness, and colicky pain after either drug. Continuous pain values were significantly lower in the OCT group than in the SB group at T2 and T3 (P < 0.05). CONCLUSIONS: At the doses used in this study, OCT was more effective than SB in controlling gastrointestinal symptoms of bowel obstruction. Further studies are necessary to understand the role of hydration more clearly in such a clinical situation.
Asunto(s)
Bromuro de Butilescopolamonio/uso terapéutico , Obstrucción Intestinal/tratamiento farmacológico , Neoplasias Hepáticas/complicaciones , Octreótido/uso terapéutico , Neoplasias Ováricas/complicaciones , Neoplasias Peritoneales/complicaciones , Neoplasias Pleurales/complicaciones , Femenino , Estudios de Seguimiento , Fármacos Gastrointestinales/uso terapéutico , Humanos , Obstrucción Intestinal/etiología , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Parasimpatolíticos/uso terapéutico , Neoplasias Peritoneales/secundario , Neoplasias Pleurales/secundario , Pronóstico , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The prognostic value of lymph node ratio (LNR) in pancreatic cancer remains controversial. In the current retrospective study, we assessed the value of LNR on predicting the survival of postoperative patients with pancreatic cancer. METHODS: Medical records of patients who underwent pancreatic resection for pancreatic cancer in the department of general surgery, Qilu Hospital, Shandong University were reviewed retrospectively. Demographic, clinicopathological, tumor-specific data, and histopathological reports were collected. Univariate and multivariate survival analyses were performed. RESULTS: A total of 83 patients with pancreatic cancer were collected. The mean number of examined LN was 8.2 ± 6.1 (0 to 26). Differential degree (low) (P = 0.019, hazard ratio (HR) = 2.276, 95% confidence interval (CI): 1.171 to 4.424) and LNR >0.2 (P = 0.018, HR = 2.685, 95% CI: 1.253 to 5.756) were independent adverse prognostic factors according to the multivariate survival analysis. CONCLUSIONS: Our study indicated that LNR >0.2 was an independent adverse prognostic factor for pancreatic cancer, which may provide important information for prognostic assessment.