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The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.
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The deliberate pork adulteration with lymph nodes is a common adulteration phenomenon, and it poses a serious threat to public health and food safety. An untargeted metabolomics and lipidomics approach based on ultrahigh performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap high resolution mass spectrometry (MS) was used to distinguish lymph nodes from minced pork. The principal component analysis and orthogonal projection to latent structures discriminant analysis models were established with the good of fitness and predictivity. The results showed that there were significant differences in metabolites and lipids between lymph nodes and pork. A total of 16 significantly differentiated metabolites were identified, of which 1-palmitoylglycerophosphocholine, 12,13-dihydroxy-9-octadecenoic acid, and prostaglandin E2 (PGE2) were positively correlated with lymph node content and were identified as potential markers of lymph nodes. These three markers were combined to create a binary logistic regression model, and a combined-factor exceeding 0.75 was ultimately identified as a marker for pork adulteration with lymph nodes. The desorption electrospray ionization-MS images showed that PGE2 had a higher relative abundance in the lymph node region than in adjacent non-lymph node regions, indicating that PGE2 was a marker that contributed significantly for identifying lymph nodes adulteration into pork. Our results provide a theoretical basis for identifying lymph node adulteration, which will contribute to combating fraud in the meat industry.
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Carne de Cerdo , Carne Roja , Animales , Porcinos , Cromatografía Líquida de Alta Presión/métodos , Lipidómica , Cromatografía Liquida/métodos , Metabolómica/métodosRESUMEN
OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: ⢠The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. ⢠Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. ⢠The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.
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Neoplasias de los Conductos Biliares , Tumor de Klatskin , Humanos , Masculino , Persona de Mediana Edad , Metástasis Linfática/patología , Tumor de Klatskin/diagnóstico por imagen , Tumor de Klatskin/cirugía , Radiómica , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Ganglios Linfáticos/patología , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patologíaRESUMEN
Purpose: The study aimed to construct and evaluate a CT-Based radiomics model for noninvasive detecting perineural invasion (PNI) of perihilar cholangiocarcinoma (pCCA) preoperatively. Materials and Methods: From February 2012 to October 2021, a total of 161 patients with pCCA who underwent resection were retrospectively enrolled in this study. Patients were allocated into the training cohort and the validation cohort according to the diagnostic time. Venous phase images of contrast-enhanced CT were used for radiomics analysis. The intraclass correlation efficient (ICC), the correlation analysis, and the least absolute shrinkage and selection operator (LASSO) regression were applied to select radiomics features and built radiomics signature. Logistic regression analyses were performed to establish a clinical model, a radiomics model, and a combined model. The performance of the predictive models was measured by area under the receiver operating characteristic curve (AUC), and pairwise ROC comparisons between models were tested using the Delong method. Finally, the model with the best performance was presented as a nomogram, and its calibration and clinical usefulness were assessed. Results: Finally, 15 radiomics features were selected to build a radiomics signature, and three models were developed through logistic regression. In the training cohort, the combined model showed a higher predictive capability (AUC = 0.950) than the radiomics model and the clinical model (AUC: radiomics = 0.914, clinical = 0.756). However, in the validation cohort, the AUC of the radiomics model (AUC = 0.885) was significantly higher than the other two models (AUC: combined = 0.791, clinical = 0.567). After comprehensive consideration, the radiomics model was chosen to develop the nomogram. The calibration curve and decision curve analysis (DCA) suggested that the nomogram had a good consistency and clinical utility. Conclusion: We developed a CT-based radiomics model with good performance to noninvasively predict PNI of pCCA preoperatively.
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BACKGROUND: There is a lack of data on drug-related problems (DRPs) occurring in nephrology department in China. The objective of this study was to identify and categorize the types and causes of DRPs and to assess their severity. DRPs were examined by clinical pharmacists and the results of their interventions were rated. METHODS: Clinical pharmacists reviewed all medication orders for patients and documented clinical pharmacy services within a nine-month study period. The Pharmaceutical Care Network Europe (PCNE) classification (Version 9.00) was used to identify DRPs. Our Primary outcomes measured the number, causes, types, potential hazards of DRPs and the types and success rate of intervention. RESULTS: Admission medication reconciliation data of 113 patients with chronic kidney disease (CKD) were collected and all of the medications were reviewed retrospectively. Exclude 26 patients who did not occurred DRPs, 87 patients (77%) identified 101 DRPs. The average DRP number per patient was 1.16. The most common type of problem was "treatment effectiveness P1" (84.16%; 85/101). The most common causes were "drug selection C1" (36.00%; 45/125), "dose selection C3" (29.60%; 37/125), and "patient related C7" (26.40%; 33/125). Clinical pharmacists totally proposed 249 interventions, of which 190 (76.31%) were fully accepted and implemented. CONCLUSIONS: DRPs are common among CKD patients in the nephrology department. Hence the necessity for pharmaceutical care to be improved to ensure the ongoing safety of patients.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Nefrología , Preparaciones Farmacéuticas , Humanos , Farmacéuticos , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
Mycotic vaginitis is a common and frequently-occurring gynaecopathia and easy to attack repeatedly, so painful to patients. In this study, the authors observed the clinical efficacy of Sophora gel combined with Fluconazole capsules in treating mycotic vaginitis, in order to seek an effective method for treating mycotic vaginitis. Totally 85 patients with mycotic vaginitis treated in our hospital between December 2012 and July 2014 were randomly divided into the treatment group (43 patients) and the control group (42 patients). The treatment group was given vaginally Sophora gel (one piece every night for 14 days) and orally Fluconazole capsules (150 mg, once every three days, four times in total); The control group was only administered with Fluconazole capsules. The total efficacy, cure rate, recurrence rate and clinical symptom improvements of the two groups were observed. The results show that the total efficacy, the cure rate and the recurrence rate of the treatment group vs. the control group were respectively 97.7%, 90.7% and 2.6% vs. 83.3%, 71.4% and 20.0%, with statistical significance in their differences (P < 0.05). The treatment group showed reduced leucorrhea, pruritus vulvae disappearance and earlier mucosal hyperemia disappearance than the control group, with statistical significance in their differences (P < 0.05). In conclusion Sophora gel combined with Fluconazole capsules can improve antifungal activity of drugs, relieve clinical symptoms, shorten the course of disease, enhance the cure rate and reduce the recurrence rate; So this therapy can be widely applied in clinic.
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Antifúngicos/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Fluconazol/administración & dosificación , Micosis/tratamiento farmacológico , Sophora/química , Vaginitis/tratamiento farmacológico , Adulto , Cápsulas/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Resultado del Tratamiento , Adulto JovenRESUMEN
Three new phenolic compounds (1-3), together with 16 known compounds (4-19), were isolated from the roots of Glycyrrhiza yunnanensis Cheng f. et L. K. Dai. On the basis of 1D and 2D NMR, HR-ESI-MS, and circular dichroism (CD) spectroscopic analysis, structures of the new compounds were elucidated as 2-(2'-methoxy-4'-hydroxy)-aryl-3-methy-6-hydroxy-benzofuran (1), (2S)-6,7-(2,2-dimethyldihydropyrano)-8-prenyl-4'-hydroxyflavanone (2), and 6-prenyl-7,3',4'-trihydroxyflavone (3). Compounds 1, 3, 5, 12, 14, 15 and 16 showed antioxidant activity by an ABTS-based assay.
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Antioxidantes/aislamiento & purificación , Glycyrrhiza/química , Fenoles/aislamiento & purificación , Estructura Molecular , Raíces de Plantas/química , Plantas Medicinales/químicaRESUMEN
OBJECTIVE: To provide evidence for further reducing the maternal mortality rate (MMR) through analyzing the causes of death and influencing factors on the issue. METHODS: Every maternal death from 1996 to 2010 was audited by experts and relevant information was collected and analyzed, retrospectively. RESULTS: (1) The overall MMR among Beijing residents was 20.2 per 100 000 live births in 1996 - 2000 while decreased to 14.2 per 100 000 live births from 2006 to 2010. At the same time, the MMR of migrating people decreased from 47.7 to 15.2 per 100 000 live births. (2) The proportion of women having received middle school education and above, increased from 59.8% to 78.8% and the non-prenatal care maternal ratio decreased from 39.1% to 12.7%. (3) Among the 349 deaths in the period of 1996 - 2010, 209 (59.9%) were caused by direct obstetric reasons. Proportion of obstetric hemorrhage declined from 14.4% to 9.2% and the amniotic fluid embolism declined from 20.7% to 15.0%. Prolific, non-prenatal care and private clinics/home deliveries were important factors on direct obstetric reasons. 71.4% maternal mortality of indirect causes appeared abnormal during pregnancy. (4) The WHO twelve-grade classification standard on maternal deaths was adopted. Our data showed that the main reasons causing maternal deaths of Beijing residents were related to the skills of medical staffs (62.4%) and healthcare management (19.7%). The main reasons of maternal deaths among migrating people would include: poor knowledge (41.4%), inappropriate attitude (32.3%) and resources of the families (24.0%). CONCLUSION: The MMR in Beijing continuously declined from 1996 to 2010. However, in order to keep up with the changing causes related to maternal deaths as well as to the increasing service requirements, it is necessary to develop a new model on service and management of the issue.
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Mortalidad Materna , Adulto , Causas de Muerte , China/epidemiología , Embolia de Líquido Amniótico/mortalidad , Femenino , Humanos , Servicios de Salud Materna/estadística & datos numéricos , Complicaciones del Trabajo de Parto/mortalidad , Embarazo , Estudios Retrospectivos , Adulto JovenAsunto(s)
Embarazo Ectópico/mortalidad , Adulto , Causas de Muerte , China , Femenino , Humanos , Mortalidad Materna , EmbarazoRESUMEN
OBJECTIVE: To analysis the trend of maternal death time and explore the impact of the variety of death causes and birth place to maternal death time. METHODS: According to the data provided by Beijing Maternal and Children Health Hospital, the 372 death cases of pregnant and lying-in women from 1995 to 2010, a retrospective study was performed to analyze the death causes, maternal death time and the influencing factors. RESULTS: The MMR declined from 27.9 per 100 000 live births from 1995 to 2000 to 14.8 per 100 000 live births from 2006 to 2010, with a decline of 46.9%. Among the maternal death within 24 hours of delivery, 79.7% (106/133) died of obstetric hemorrhage, hypertensive disorder complicating pregnancy and amniotic fluid embolism. It took up 47.8% (64/134) from 1995 to 2000, reduced to 37.5% (45/120) from 2006 to 2010. At the same time, the maternal mortality ratio within 24 hours reduced from 40.2%(54/134) to 28.3% (34/120), the variation of death time was consistent with the causes of maternal mortality (χ² = 59.109, P < 0.05). Indirect obstetric causes increased significantly from 2006 to 2010, 53.2% (33/62) of pregnant women with heart disease, cerebrovascular disease and pulmonary embolism died in prenatal or more than 120 hours postnatal. Among the maternal death delved in hospital, 29.0% (29/100) died within 24 hours, 52 cases delved at home or in private clinics, 43 cases (82.6%) died within 24 h postnatal. There were significant differences between birth place and death time (χ² = 24.500, P < 0.05). CONCLUSION: Maternal death time changed from 24 hours of delivery to prenatal or postnatal a long time. The maternal mortality causes and hospital delivery is an important factor affecting maternal time.
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Mortalidad Materna/tendencias , Complicaciones del Embarazo/mortalidad , Causas de Muerte , China , Femenino , Humanos , Servicios de Salud Materna , EmbarazoRESUMEN
BACKGROUND: The aim of this study was to investigate the post-treatment effect of intravenous hyperoxygenated solution (HOS) on pulmonary parameters in rabbits whole-body-exposed to the toxic gas phosgene. MATERIALS AND METHODS: Twenty-four New Zealand rabbits were divided into four groups randomly: rabbits were exposed whole-body to either filtered room air or 539 ppm phosgene for 5 minutes followed by room air washout for 5 minutes. Phosgene-exposed group (exposed to phosgene without treatment, PH group); Control group (exposed to air, Control group); Lactate Ringer's solution (LRS)-treated group (intravenous infusion of LRS by 30 ml·kg-1 after phosgene exposure, LRS group); Hyperoxygenated solution (HOS)-treated group (intravenous infusion of HOS after phosgene exposure by 30 mL·kg-1, HOS group). Arterial blood was collected for blood gas analysis at 1, 3, 8, and 12 hours after phosgene or air exposure. Rabbits were put to death 12 hours after exposure. Lung edema was assessed gravimetrically by measuring tissue wet/dry weight ratio (W/D) and lung coefficient (LC). Bronchoalveolar lavage (BAL) was performed and fluid was analyzed for total maloaldehyde (MDA), glutathione peroxidase (GSH-Px), and protein concentration. Lungs were perfused with saline to remove blood, snap-frozen in liquid nitrogen (N2), analyzed for tissue reduced glutathione (GSH) and oxidized glutathione (GSSG). Parts of lung tissues were reserved for histopathology examination. RESULTS: In the PH, LRS, and HOS groups, phosgene inhalation caused serious lung edema, W/D and LC, lung tissue GSSG, BALF MDA, and protein content increased significantly. Meanwhile, PaO2, lung tissue GSH, and BALF GSH-Px decreased markedly. However, after HOS treatment in the HOS group, PaO2 was clearly higher than that in the PH group and LRS group at 3, 8, 12 hours (P < 0.01). W/D and LC, lung tissue GSSG, BALF MDA, and protein content in the HOS group were apparently lower than that in the PH group and LRS group (P < 0.01). In the HOS group, lung tissue GSH and BALF GSH-Px increased compared with both PH and LRS group, respectively. There was no difference on lung tissue GSH among the PH, LRS, and HOS groups (P > 0.05). CONCLUSIONS: Intravenous HOS infusion after phosgene exposure can clearly lessen phosgene-induced lung edema formation, lipid peroxidatic reaction, and ameliorate hypoxemia associated with phosgenismus; it is a safe, simple, and effective measure to protect animals from phosgene-induced lung injury.
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Lesión Pulmonar Aguda/terapia , Sustancias para la Guerra Química/toxicidad , Oxígeno/farmacología , Fosgeno/toxicidad , Edema Pulmonar/terapia , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Animales , Líquido del Lavado Bronquioalveolar , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Infusiones Intravenosas , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Malondialdehído/metabolismo , Oxígeno/sangre , Edema Pulmonar/inducido químicamente , Edema Pulmonar/patología , Conejos , Soluciones/farmacologíaRESUMEN
Taking 21 representative urban greening species in Xi' an as test objects, their leaf dust-capturing capability was determined by artificial dust-deposition method, and the relationships between the dust-capturing capability and leaf surface features, e.g., trichomes, wettability, surface free energy and its polar and dispersive components on dust-capturing capability were studied. For the tested 21 species, their maximum leaf dust-capturing capability was 0.8-38.6 g x m(-2), and there was a significant difference among them, with the greatest varoiation up to forty times. The amount, distribution, and morphology of trichomes had great influence on the leaf dust-capturing capability, possibly due to the different action patterns between trichomes and particulate matters. There was a significant negative relationship between leaf contact angle and maximum leaf dust-capturing capability (r = -0.523), except for four species whose leaf surface has trichomes. For wettable leaves, their maximum dust-capturing capacity ranged from 2.0 to 8.0 g x m(-2), but for nonwettable leaves, their maximum dust-capturing capacity was below 2.0 g x m(-2). The leaf surface free energy was mainly manifested in the action of dispersive component while contribution of polar free energy was lower than 20%, which could be related to the existence of non-polar or weakly polar substances on leaf surface. The leaf surface free energy and its dispersive component had a significant positive correlation (r = 0.500, 0.572) with the maximum leaf dust-capturing capability, but the positive correlation between polar free energy and maximum dust-capturing capability was not significant (r = 0.244).