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Cancer cells use multiple mechanisms to evade the effects of glutamine metabolism inhibitors. The pathways that govern responses to alterations in glutamine availability within the tumor may represent therapeutic targets for combinatorial strategies with these inhibitors. Here, we showed that targeting glutamine utilization stimulated Yes-associated protein (YAP) signaling in cancer cells by reducing cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-dependent phosphorylation of large tumor suppressor (LATS). Elevated YAP activation induced extracellular matrix (ECM) deposition by increasing secretion of connective tissue growth factor (CTGF) that promoted production of fibronectin and collagen by surrounding fibroblasts. Consequently, inhibiting YAP synergized with inhibition of glutamine utilization to effectively suppress tumor growth in vivo, along with a concurrent decrease in ECM deposition. Blocking ECM remodeling also augmented the tumor suppressive effects of the glutamine utilization inhibitor. Collectively, these data reveal mechanisms by which targeting glutamine utilization increases ECM accumulation and identify potential strategies to reduce ECM levels and increase the efficacy of glutamine metabolism inhibitors.
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Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.
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Microglia regulate synaptic function in various ways, including the microglial displacement of the surrounding GABAergic synapses, which provides important neuroprotection from certain diseases. However, the physiological role and underlying mechanisms of microglial synaptic displacement remain unclear. In this study, we observed that microglia exhibited heterogeneity during the displacement of GABAergic synapses surrounding neuronal soma in different cortical regions under physiological conditions. Through three-dimensional reconstruction, in vitro co-culture, two-photon calcium imaging, and local field potentials recording, we found that IL-1ß negatively modulated microglial synaptic displacement to coordinate regional heterogeneity in the motor cortex, which impacted the homeostasis of the neural network and improved motor learning ability. We used the Cre-Loxp system and found that IL-1R1 on glutamatergic neurons, rather than that on microglia or GABAergic neurons, mediated the negative effect of IL-1ß on synaptic displacement. This study demonstrates that IL-1ß is critical for the regional heterogeneity of synaptic displacement by coordinating different actions of neurons and microglia via IL-1R1, which impacts both neural network homeostasis and motor learning ability. It provides a theoretical basis for elucidating the physiological role and mechanism of microglial displacement of GABAergic synapses.
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Aprendizaje , Microglía , Calcio , Neuronas GABAérgicas , Interleucina-1beta , SinapsisRESUMEN
SMAD4 is a tumour suppressor and an important regulator of tumour immune scape which is downregulated in cholangiocarcinoma (CCA). STING1 is a vital sensing factor of abnormal DNA; however, the correlation between SMAD4 and STING1 and the role of the SMAD4-STING1 interaction in the progression of CCA have not yet been evaluated. Public database was analysed to reveal the expression of SMAD4 and STING1. A cohort comprising 50 iCCA, 113 pCCA and 119 dCCA patients was assembled for the study. Immunohistochemistry was employed to evaluate the expression levels of STING1 and SMAD4. In vitro transwell and CCK8 assays, along with luciferase reporter assay, were conducted to analyse the potential regulatory mechanisms of SMAD4 on the expression of STING1. Expression of SMAD4 and STING1 were downregulated in CCA tumours and STING1 expression correlated with SMAD4 expression. The overexpression of SMAD4 was found to suppress the migration, invasion and proliferation capabilities of CCA cells; whereas, the knockdown of SMAD4 enhanced these abilities. Furthermore, it was observed that SMAD4 translocated into the nucleus following TGF-ß1 stimulation. Knockdown of SMAD4 resulted in the inhibition of STING1 transcriptional activity, whereas the overexpression of SMAD4 promoted the transcriptional activity of STING1. Clinically, low STING1 and SMAD4 expression indicated poor prognosis in CCA, and simultaneously low expression of STING1 and SMAD4 predicts poorer patient survival. SMAD4 regulates the expression of STING1 through its transcription regulating function. Dual low expression of STING1 and SMAD4 had more power in predicting patient survival. These results indicate that SMAD4-silenced CCA may downregulate its STING1 expression to adapt to the immune system.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Proteína Smad4 , Humanos , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Colangiocarcinoma/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteína Smad4/genética , Proteína Smad4/metabolismoRESUMEN
Biliary cystadenoma (also called mucinous cystic neoplasm with low-grade intraepithelial neoplasia) is a rare cystic tumor that arises from the biliary epithelium. The cause of biliary cystadenoma is still unclear. Jaundice is a rare presentation of intrahepatic biliary cystadenoma, which can lead to a diagnostic dilemma. Herein, we present a case of intrahepatic biliary cystadenoma that primarily exhibited as jaundice. A 56-year-old woman has suffered from yellow staining of her skin and sclera for more than 1 month. She had a poor appetite and mild epigastric pain. Laboratory examination showed elevated levels of total bilirubin and elevated carbohydrate antigen 19-9 (CA19-9). A contrast-enhanced computed tomography of the abdomen showed a 7.4 * 5.3-cm, oval, low-density lesion in the left liver parenchyma with a clear boundary and visible septa. The common bile duct was obviously dilated with wall thickening. On magnetic resonance imaging, the lesion in the liver showed a multilocular cystic, unenhanced long T2 signal. There was local thickening of the common bile duct wall with short T2-like filling defects and high signal intensity on diffusion-weighted imaging (DWI). The patient had no history of other malignant tumors and adjuvant therapy such as radiotherapy and chemotherapy. She was clinically suspected of having either biliary cystadenoma or a malignancy; hence, resection was performed. Macroscopically, the excised tissue specimen showed a polypoid mass in the common bile duct, which extended along the bile duct to the intrahepatic bile duct. There was a cystic and solid mass in the left liver with yellow turbid fluid, which was associated with the polypoid mass in the common bile duct. Histopathology suggests mucinous cystadenoma of the liver and hilar bile duct. The differential diagnosis of biliary cystadenoma and treatment selection have been discussed.
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Cholangiocarcinoma (CCA) is a highly malignant tumor of the hepatobiliary system that has failed to respond to many traditional therapies to a certain extent, including surgery, chemotherapy and radiotherapy. In recent years, the new therapeutic schemes based on immunology have fundamentally changed the systemic treatment of various malignant tumors to a certain extent. In view of the immunogenicity of CCA, during the occurrence and development of CCA, some immunosuppressive substances are released from cells and immunosuppressive microenvironment is formed to promote the escape immune response of its own cells, thus enhancing the malignancy of the tumor and reducing the sensitivity of the tumor to drugs. Some immunotherapy regimens for cholangiocarcinoma have produced good clinical effects. Immunotherapy has more precise characteristics and less adverse reactions compared with traditional treatment approaches. However, due to the unique immune characteristics of CCA, some patients with CCA may not benefit in the long term or not benefit at all after current immunotherapy. At present, the immunotherapy of CCA that have been clinically studied mainly include molecular therapy and cell therapy. In this article, we generalized and summarized the current status of immunotherapy strategies including molecular therapy and cell therapy in CCA in clinical studies, and we outlined our understanding of how to enhance the clinical application of these immunotherapy strategies.
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In this communication, a palladium-catalyzed regio- and stereoselective carbonylation of 2-trifluoromethyl-1,3-enynes to afford multisubstituted conjugated dienes has been realized. This protocol features excellent regio- and exclusive (E)-stereoselectivity and a broad substrate scope with both amines and alcohols as the suitable reaction partners and has shown promising functional group tolerance.
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Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.
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Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Humanos , Bilis , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/patología , Biomarcadores , Conductos Biliares Intrahepáticos/patología , InmunidadRESUMEN
Purpose: This study aims to identify key genes in slow transit constipation (STC). We also sought to explore the potential link between STC and colorectal cancer. Patients and Methods: mRNA expression profiles were obtained by RNA sequencing, and differentially expressed genes were identified. Functional enrichment analysis and a protein-protein interaction (PPI) network was explored, and differentially expressed genes common to STC and colorectal cancer were examined. Analysis of the effect of constipation and colorectal cancer common genes on the overall survival of colorectal cancer patients based on GEPIA database. Results: Functional enrichment showed that significantly different genes are related to lymphocyte chemotaxis, positive regulation of inflammatory response, cellular response to tumor necrosis factor, extracellular region, extracellular space and chemokine activity. The hub gene for STC was found in the PPI network. In addition, AQP8 and CFD were common differential genes for STC and colorectal cancer. AQP8 affects overall survival in patients with colorectal cancer. Conclusion: Our findings will contribute to understanding the pathology of STC at the molecular level, with the first discovery that AQP8 may be a hub gene in the transition from STC to colorectal cancer.
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A pipeline carrying unconventional oil and gas (OG) wastewater spilled approximately 11 million liters of wastewater into Blacktail Creek, North Dakota, USA. Flow of the mix of stream water and wastewater down the channel resulted in storage of contaminants in the hyporheic zone and along the banks, providing a long-term source of wastewater constituents to the stream. A multi-level investigation was used to assess the potential effects of oil and brine spills on aquatic life. In this study, we used a combination of experiments using a native fish species, Fathead Minnow (Pimephales promelas), field sampling of the microbial community structure, and measures of estrogenicity. The fish investigation included in situ experiments and experiments with collected site water. Estrogenicity was measured in collected site water samples, and microbial community analyses were conducted on collected sediments. During the initial post-spill investigation, February 2015, performing in situ fish bioassays was impossible because of ice conditions. However, microbial community (e.g., the presence of members of the Halomonadaceae, a family that is indicative of elevated salinity) and estrogenicity differences were compared to reference sites and point to early biological effects of the spill. We noted water column effects on in situ fish survival 6 months post-spill during June 2015. At that time, total dissolved ammonium (sum of ammonium and ammonia, TAN) was 4.41 mg NH4/L with an associated NH3 of 1.09 mg/L, a concentration greater than the water quality criteria established to protect aquatic life. Biological measurements in the sediment defined early and long-lasting effects of the spill on aquatic resources. The microbial community structure was affected during all sampling events. Therefore, sediment may act as a sink for constituents spilled and as such provide an indication of continued and cumulative effects post-spill. However, lack of later water column effects may reflect pulse hyporheic flow of ammonia from shallow ground water. Combining fish toxicological, microbial community structure and estrogenicity information provides a complete ecological investigation that defines potential influences of contaminants at organismal, population, and community levels. In general, in situ bioassays have implications for the individual survival and changes at the population level, microbial community structure defines potential changes at the community level, and estrogenicity measurements define changes at the individual and molecular level. By understanding effects at these various levels of biological organization, natural resource managers can interpret how a course of action, especially for remediation/restoration, might affect a larger group of organisms in the system. The current work also reviews potential effects of additional constituents defined during chemistry investigations on aquatic resources.
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Compuestos de Amonio , Cyprinidae , Percas , Contaminantes Químicos del Agua , Animales , Amoníaco/análisis , Compuestos de Amonio/análisis , Cyprinidae/fisiología , Hielo/análisis , North Dakota , Ríos/química , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Nitrógeno/análisisRESUMEN
Cervical spondylotic myelopathy (CSM) is common in elderly people and severe CSM patients are recommended to receive surgery. However, in some cases, surgery may fail to improve the patients' symptoms. An 80-year-old man diagnosed with CSM complained of right hemiplegia and right arm and leg pain with the presence of a Foley catheter, despite treatment with laminectomy and laminoplasty. Acupuncture, bee venom pharmacopuncture, and herbal medicine were administered for 129 days. As a result, manual muscle testing (MMT) and the Modified Barthel Index (MBI) improved, the pain in his right arm and leg decreased, and he was able to urinate by himself. This case report implies that integrative Korean medicine (IKM) can be an option for patients suffering from muscular weakness resulting from myelopathy.
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Oil and gas extraction in the Prairie Pothole Region (PPR) of the northern USA has resulted in elevated chloride concentrations in ground and surface water due to widespread contamination with highly saline produced water, or brine. The toxicity of chloride is poorly understood in the high hardness waters characteristic of the region. We evaluated the toxicity of chloride to two endemic species, Daphnia magna (water flea) and Lemna gibba (duckweed), exposed in field-collected waters (hardness ~ 3000 mg/L as CaCO3) and reconstituted waters (hardness 370 mg/L as CaCO3) intended to mimic PPR background waters. We also investigated the role of chloride in the toxicity of water reconstituted to mimic legacy brine-contaminated wetlands, using two populations of native Pseudacris maculata (Boreal Chorus Frog). Chloride toxicity was similar in field-collected and reconstituted waters for both D. magna (LC50s 3070-3788 mg Cl-1/L) and L. gibba (IC50s 2441-2887). Although hardness can ameliorate chloride toxicity at low to high hardness, we did not observe additional protection as hardness increased from 370 to ~ 3000 mg/L. In P. maculata exposures, chloride did not fully explain toxicity. Chloride sensitivity also differed between populations, with mortality at 2000 mg Cl-/L in one population but not the other, and population-specific growth responses. Overall, these results (1) document toxicity to native species at chloride concentrations occurring in the PPR, (2) indicate that very high hardness in the region's waters may not provide additional protection against chloride and (3) highlight challenges of brine investigations, including whether surrogate study populations are representative of local populations.
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Cloruros , Pradera , Animales , Cloruros/toxicidad , Daphnia , Agua Dulce , HumedalesRESUMEN
We demonstrate coupling between the motions of two independently trapped ions with a separation distance of 620 µm. The ion-ion interaction is enhanced via a room-temperature electrically floating metallic wire which connects two surface traps. Tuning the motion of both ions into resonance, we show flow of energy with a coupling rate of 11 Hz. Quantum-coherent coupling is hindered by strong surface electric-field noise in our device. Our ion-wire-ion system demonstrates that room-temperature conductors can be used to mediate and tune interactions between independently trapped charges over distances beyond those achievable with free-space dipole-dipole coupling. This technology may be used to sympathetically cool or entangle remotely trapped charges and enable coupling between disparate physical systems.
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The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.
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Neoplasias Colorrectales , Microbiota , Ubiquitina-Proteína Ligasas/metabolismo , Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Propionatos , Regulación hacia ArribaRESUMEN
PURPOSE: The programmed death protein 1 (PD-1) pathway is the critical mechanism in development of hepatocellular carcinoma (HCC). The present study analyzed the prognostic impact of pretransplant serum soluble PD-1 (sPD-1) concentration and α-FP-des-γ-carboxyprothrombin-tumor volume (ADV) score in patients with previously untreated HCC undergone liver transplantation (LT). METHODS: This retrospective single-center study enrolled 100 patients with HCC who underwent living donor LT from 2010 to 2016. Concentrations of sPD-1 were measured in stored serum samples. RESULTS: Receiver operating characteristic curve analysis of 2-year tumor recurrence resulted in an sPD-1 cutoff of 177.1 µg/mL, which was associated with higher rates of tumor recurrence (P = 0.022), but not with overall patient survival (P = 0.460). The derived cutoff for pretransplant ADV score was 5.4log, which was associated with higher tumor recurrence rate (P < 0.001) and lower overall patient survival rate (P < 0.001). Both sPD-1 of >177.1 µg/mL (hazard ratio [HR], 2.26; P = 0.020) and pretransplant ADV score of >5.4log (HR, 3.56; P < 0.001) were independent risk factors for posttransplant HCC recurrence. The combination of these 2 factors enabled the stratification of patients into 3 groups, with groups having 0, 1, and 2 risk factors differing significantly in the prognosis of tumor recurrence (P < 0.001) and overall patient survival (P = 0.006). CONCLUSION: Both sPD-1 concentration and ADV score have prognostic impacts in patients who underwent LT for untreated HCCs. These factors, both individually and combined, can help in predicting posttransplant prognosis.
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PURPOSE: To analyze the nutritional status of patients with malignant oral and maxillofacial neoplasms complicated with diabetes mellitus during perioperative period. METHODS: Sixty-four patients with malignant oral and maxillofacial neoplasms complicated with diabetes mellitus were collected. Fasting venous blood of patients was extracted on the morning of the day before surgery and then at the 1st, 3rd and 7th day after surgery, respectively. The hemoglobin (Hb), total protein (TP), pre-albumin (PA), lymphocyte count (L), creatinine (Scr), uric acid (UA), urea nitrogen (BUN), glomerular filtration rate (EGFR_EPI_C), white blood cells (WBC) of the patients were detected. The intake of enteral nutrition on the 7th day after operation was investigated. The correlation between nutritional status and the length of stay was analyzed. SPSS 23.0 software package was used for statistical analysis. RESULTS: Compared with the indicators before surgery, the values of TP, ALB, PA, Hb were decreased significantly after surgery in all groups(P<0.05). The level of TP on postoperative day 7 was significantly higher than that on postoperative day 1 and postoperative day 3(P<0.05). The PA level on the third day after surgery was significantly lower than that on the first day after surgery(P<0.05). The Hb level on the 7th and 3rd day after surgery was significantly lower than that on the 1st day after surgery (P<0.05). The level of L decreased significantly in each group after surgery compared with the level before surgery(P<0.05), and gradually increased in each group after surgery, with significant difference among each two groups (P<0.05). Compared with preoperative value, blood Scr was significantly decreased in all groups after surgery (P<0.05), the UA level after surgery was significantly lower than the preoperative level in all groups(P<0.05), and at the 3rd day after surgery was significantly lower than at the 1st day after surgery(P<0.05). After surgery, the eGFR_EPI_c level was significantly higher than the level before surgery in all groups (P<0.05), and at the 7th day after surgery was significantly higher than at the 1st day after surgery (P<0.05). The level of WBC in all patients after surgery was significantly higher than that before surgery(P<0.05), and the level at the 3rd and 7th day after surgery was significantly higher than that at the 1st day after surgery(P<0.05). At the 7th day after surgery, the energy and protein intakes of the patients were significantly lower than the recommendations. There was positive correlation between preoperative BMI and TP, ALB levels at the 1st postoperative day and the TP level at 3rd postoperative day(P<0.05). There was no direct correlation between preoperative BMI and the length of postoperative hospital stay (P>0.05). The length of postoperative hospital stay was negatively correlated with the age and negatively with TP and ALB levels at the 1st postoperative day(P<0.05). CONCLUSIONS: Early postoperative nutritional status of patients with malignant oral and maxillofacial neoplasms complicated with diabetes mellitus decreased significantly. The energy and protein intakes of the patients are significantly lower than the recommendations. The length of postoperative hospital stay is negatively correlated with early postoperative nutritional status and age.
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Diabetes Mellitus , Neoplasias , Humanos , Tiempo de Internación , Recuento de Leucocitos , Estado NutricionalRESUMEN
BACKGROUND: Twin pregnancies continue to increase worldwide; however, the current clinical prenatal evaluation for the intrauterine growth of twins still relies on the growth standards of singletons. We attempted to establish a set of fetal biometric references for Chinese twin pregnancies, stratified by chorionicity and conception mode as spontaneously conceived monochorionic diamniotic (SC-MCDA), spontaneously conceived dichorionic diamniotic (SC-DCDA), and assisted reproductive technology dichorionic diamniotic (ART-DCDA) twins. METHODS: From 2016 to 2019, the ultrasonographic fetal biometric measurements were longitudinally collected in pregnant women, including fetal weight, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length. The linear mixed models were used to test the difference of growth patterns between groups, and the growth curve of each biometric parameter was modeled by a generalized additive model for location scale and shape. RESULTS: A total of 929 twin pregnant women and 2019 singleton pregnant women, met the inclusion criteria. Among twin pregnancies, 148 were SC-MCDA, 215 were SC-DCDA, and 566 were ART-DCDA twins. Overall, SC-DCDA twins grew faster than SC-MCDA twins, while slower than ART-DCDA twins (all Pâ<â0.05), and all of the three groups showed significant differences comparing with singletons, especially during the third trimester. Hence, the customized fetal growth charts of each fetal biometric parameter were, respectively, constructed for SC-MCDA, SC-DCDA, and ART-DCDA twins. CONCLUSIONS: The fetal biometric trajectories demonstrated characteristic patterns according to chorionicity and conception mode. To fill the gap, we modeled fetal biometric parameters for Chinese SC-MCDA, SC-DCDA, and ART-DCDA twin pregnancies, hoping to provide a reference for the further establishment of fetal growth reference values for Chinese twin fetuses.
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Desarrollo Fetal , Gráficos de Crecimiento , China , Femenino , Humanos , Embarazo , Embarazo Gemelar , Estudios Retrospectivos , Ultrasonografía PrenatalRESUMEN
BACKGROUD: Reliable scapular upward rotation and anterior-posterior tilt data are required for patients with subacromial impingement syndrome (SIS). Only a few studies have explored the reliability of such measurements derived using a modified inclinometer. OBJECTIVES: To determine the relative and absolute reliability of scapular upward rotation and anterior-posterior tilt measurements derived using a modified digital inclinometer in patients with SIS. METHOD: Seventeen SIS patients were assessed twice within 1 week. We determined the relative and absolute measurement reliability by calculating the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimal clinically important difference (MCID). Both intra- and interrater reliability were determined. RESULTS: The intra-rater reliability (both measurements) was high (0.72-0.88), and the interrater ICC was high to excellent (0.72-0.98). Clinically acceptable SEM and MCID values were obtained for scapular upward rotation (SEM: 4.28-9.33∘, MCID: 5.1-11.3∘) and anterior-posterior tilt (SEM: 3.72-7.55∘, MCID: 2.5-10.8∘). CONCLUSIONS: Measurements of scapular upward rotation and anterior-posterior tilt using a modified digital inclinometer reliably reveal scapular position and kinematics in patients with SIS.
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Síndrome de Abducción Dolorosa del Hombro , Articulación del Hombro , Fenómenos Biomecánicos , Humanos , Rango del Movimiento Articular , Reproducibilidad de los Resultados , Rotación , EscápulaRESUMEN
Tembusu Virus (TMUV), a pathogenic member of Flavivirus family, acts as the causative agent of egg-laying and has severely threatened the duck industry over the past few years. Thus far, the pathogenicity of such virus has been extensively studied, whereas TMUV on immune system has been less comprehensively assessed, especially on ducklings that exhibit more susceptible to TMUV attack. Accordingly, in the present study, 5-day-old ducklings were infected with TMUV-TC2B (104 TCID50) via intravenous injection, and mock ones were inoculated with phosphate-buffered saline (PBS) in identical manner as control. At 1 day-post inoculation (dpi), the innate immunity was strongly activated, and reacted rapidly to TMUV invasion, which was reflected as the significantly up-regulated IFN-stimulated genes (ISGs), especially in immune organs (e.g., thymus, bursa of Fabricius (BF) and spleen). Subsequently, under the continuous monitoring, the levels of IgA, IgM and IgG acting as the representative immunoglobulins (Igs) were constantly higher than those of mock ducklings, demonstrating that humoral immunity also played a major role in anti-virus infection. Despite the immune system activated positively, TMUV still caused systemic infection, and in particular, the immune organs were subject to severe damage in the early infection. With our constant observation, the injury of spleen and BF turned out to be getting more serious, and at 6 dpi, TMUV antigen was widely detected in both of two immune organs by immunohistochemistry (IHC) and main histopathological lesion presented as lymphocytopenia. Moreover, the elevated apoptosis rate of splenic lymphocytes and the alteration of immune organ index also revealed the damage of lymphoid organs and similarly, it is worth noting that severe damages were detected in thymus of TMUV-infected ducklings as well. In brief, the present study systematically described the dynamic damage of immune system after being attacked by TMUV and presented insights into the research of pathogenicity.
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Inmunidad Adaptativa , Bolsa de Fabricio/patología , Infecciones por Flavivirus/veterinaria , Flavivirus , Bazo/patología , Timo/patología , Animales , Peso Corporal , Encéfalo/patología , Bolsa de Fabricio/virología , Patos , Infecciones por Flavivirus/inmunología , Infecciones por Flavivirus/patología , Infecciones por Flavivirus/virología , Inmunoglobulinas/sangre , Interferones/metabolismo , Riñón/patología , Hígado/patología , Pulmón/patología , Miocardio/patología , Enfermedades de las Aves de Corral/patología , Enfermedades de las Aves de Corral/virología , Bazo/virología , Timo/inmunologíaRESUMEN
AIM: To assess the potential of texture analysis (TA) applied in T1 maps and extracellular volume (ECV) obtained using cardiac magnetic resonance (CMR) in the diagnosis of hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) compared with normal controls (NC). Strain parameters were analysed to compare with final TA models. MATERIALS AND METHODS: This retrospective study included 66 HCM patients, 39 HHD patients, and 41 NC. Step-wise dimension reduction and feature selection were performed by reproducibility, machine learning, collinearity, and multivariable regression analysis to select the texture features that enable diagnosis of and differentiation between HCM and HHD. Strain parameters were calculated by short-axis and three long-axis cine sequences. RESULTS: Independent features in T1 maps and ECV analysis allowed for the differentiation between patients (HCM and HHD) and NC. Of the best-calculated model, the areas under the receiver operating curve (AUCs) were as follows: 0.969 for T1 map and 0.964 for ECV. To distinguish HCM from HHD, two independent features were screened out for both T1 and ECV maps. The AUCs were as follows: 0.793 for T1 map and 0.894 for ECV. Radial, circumferential, and longitudinal strain parameters could differentiate patients from NC, but only longitudinal strain parameters was significantly different between HCM and HHD. CONCLUSIONS: Texture analysis of T1 maps and ECV shows high accuracy in differentiating hypertrophic myocardium from NC, and HCM from HHD. Strain parameters are able to demonstrate the difference between patients and NC, but were less impressive in differentiating HCM and HHD.