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1.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(4): 364-368, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38813629

RESUMEN

OBJECTIVE: To investigate the effect of prone position on the prognosis of patients with severe pneumonia in intensive care unit (ICU). METHODS: A retrospective cohort study was conducted. The patients with severe pneumonia admitted to the ICU of Qingdao Municipal Hospital from May 2022 to August 2023 were enrolled. The general information, etiology, underlying diseases, vital signs and laboratory indicators at ICU admission, clinical treatment and prognosis during ICU hospitalization were collected. The above clinical data of patients with different prognosis were compared. Multifactorial Logistic regression analysis was used to screen the related factors affecting survival during ICU in patients with severe pneumonia. The change in oxygenation index (PaO2/FiO2) of patients with severe pneumonia were observed at 1 hour before the first prone position, 1 hour after the first prone position, and 1 hour after the end of the first prone position. The effect of prone position on oxygenation in patients with severe pneumonia was analyzed. Spearman correlation analysis was used to investigate the correlation between the duration to first prone position and the change in the PaO2/FiO2 before and after prone position in patients with severe pneumonia. RESULTS: Finally, a total of 144 patients with severe pneumonia were enrolled, 45 survived and 99 died during ICU hospitalization, with a mortality of 68.8%. Compared with the survival group, the patients in the death group were older [years old: 81.00 (70.75, 86.00) vs. 71.00 (60.50, 81.50), P < 0.01], the proportion of pre-existing lung disease, heart rate (HR), respiratory rate (RR), blood lactic acid (Lac) and the ratio of continuous renal replacement therapy (CRRT) were higher [ratio of pre-existing lung disease: 23.2% (23/99) vs. 8.9% (4/45), HR (bpm): 99.61±22.47 vs. 91.49±18.76, RR (times/min): 22.50 (19.75, 29.25) vs. 20.00 (17.50, 24.50), Lac (mmol/L): 2.00 (1.55 , 3.25) vs. 1.60 (1.20, 1.95), CRRT ratio: 25.3% (25/99) vs. 6.7% (3/45), all P < 0.05], and the proportion of prone position was lower [41.4% (41/99) vs. 68.9% (31/45), P < 0.01]. Multifactorial Logistic regression analysis showed that age [odds ratio (OR) = 0.946, 95% confidence interval (95%CI) was 0.912-0.980, P = 0.002] and Lac (OR = 0.563, 95%CI was 0.340-0.930, P = 0.025) were negatively correlated with survival during ICU hospitalization in severe pneumonia patients, while prone position was positively correlated with survival (OR = 2.551, 95%CI was 1.067-6.095, P = 0.035), indicating that prone position was beneficial for improving ICU prognosis in severe pneumonia patients. The results of PaO2/FiO2 at different time points in prone position showed that PaO2/FiO2 at 1 hour of the first prone position in the patients with severe pneumonia was significantly higher than that at 1 hour before the first prone position [mmHg (1 mmHg ≈ 0.133 kPa): 146.69 (113.92, 257.25) vs. 111.75 (70.15, 212.20), P < 0.01], indicating that the prone position had a relevant effect on the improvement of oxygenation in patients. Spearman correlation analysis showed that the duration of the first prone position in patients with severe pneumonia was significantly and positively correlated with the improvement of oxygenation at 1 hour of the first prone position (r = 0.565, P < 0.001). CONCLUSIONS: The prone position is a therapeutic measure that can independently influence the prognosis of patients with severe pneumonia during ICU hospitalization. The prone position effectively improves oxygenation in patients with severe pneumonia and the first change in oxygenation in patients is related to the duration of the prone position.


Asunto(s)
Unidades de Cuidados Intensivos , Neumonía , Humanos , Posición Prona , Estudios Retrospectivos , Neumonía/terapia , Pronóstico , Masculino , Femenino
2.
Nat Commun ; 15(1): 4580, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811566

RESUMEN

Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C2- or C1-symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies.

3.
Risk Manag Healthc Policy ; 17: 1151-1163, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737420

RESUMEN

Purpose: This study aimed to find the caregiving burden level for patients with dementia who had multiple chronic diseases by simultaneously considering both patient and caregiver factors. Participants and Methods: A cross-sectional study with 284 patients with dementia having multiple chronic diseases managed by the dementia collaborative care team at Changhua Christian Hospital in Taiwan was conducted. The input variables were from patients, such as age, gender, mood symptoms, and behavioral and psychological symptoms, and caregivers, including age, relation to the patient, caregiver's mood, and caregiving burden. The Apriori algorithm was employed to determine the association between patient and caregiver factors and different caregiving burden levels by setting up the minimum support of 1% and confidence of 90% along with lift >1. Results: When caring for patients with dementia, twenty scenarios were found for caregivers with a severe burden. In addition, 1936 scenarios were related to caregivers with a moderate-to-severe burden. Specifically, there were eight scenarios for patients with three chronic diseases which could be further categorized into five general rules. Two hundred and fifty scenarios belonging to patients with two chronic diseases could be classified into 16 different combinations from eight chronic diseases of the database. Conclusion: Caregiver's mood, patients with mild dementia, and patients aged 75-84 years were associated with a severe caregiving burden. College and above education of the caregiver, the patient aged 85 years or more, and at least one of caregiver's moods were the variables to result in a moderate-to-severe burden for caregivers caring for patients with three multiple chronic diseases. Moreover, college and above education of the caregiver, mood symptom, age of the caregiver, and age of the patient were important variables for caregivers who had a moderate-to-severe burden taking care of patients with two chronic diseases.

4.
Mater Today Bio ; 26: 101046, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38600922

RESUMEN

Owing to the tissue characteristics of tendons with few blood vessels and cells, the regeneration and repair of injured tendons can present a considerable challenge, which considerably affects the motor function of limbs and leads to serious physical and mental pain, along with an economic burden on patients. Herein, we designed and fabricated a dipeptide hydrogel (DPH) using polypeptides P11-4 and P11-8. This hydrogel exhibited self-assembly characteristics and could be administered in vitro. To endow the hydrogel with differentiation and regeneration abilities, we added different concentrations of growth differentiation factor 5 (GDF5) to form GDF5@DPH. GDF5@DPH promoted the aggregation and differentiation of tendon stem/progenitor cells and promoted the regeneration and repair of tendon cells and collagen fibers in injured areas. In addition, GDF5@DPH inhibited inflammatory reactions in the injured area. Owing to its injectable properties, DPH can jointly inhibit adhesion and scar hyperplasia between tissues caused by endogenous inflammation and exogenous surgery and can provide a favorable internal environment for the regeneration and repair of the injured area. Overall, the GDF5@DPH system exhibits considerable promise as a novel approach to treating tendon injury.

5.
Infect Drug Resist ; 17: 1073-1084, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38525478

RESUMEN

Purpose: To retrospectively analyse the different imaging manifestations of acquired immunodeficiency syndrome-associated hepatic Kaposi's sarcoma (AIDS-HKS) on CT, MRI, and Ultrasound. Patients and Methods: Eight patients were enrolled in the study. Laboratory tests of liver function were performed. The CT, MRI, and Ultrasound manifestations were reviewed by two radiologists and two sonographers, respectively. The distribution and imaging signs of AIDS-HKS were evaluated. Results: AIDS-HKS patients commonly presented multiple lesions, mainly distributed around the portal vein on CT, MRI, and Ultrasound. AIDS-HKS presented as ring enhancement in the arterial phase on contrast-enhanced CT and MRI scanning, and nodules gradually strengthen in the portal venous phase and the delayed phase. AIDS-HKS presented as intrahepatic bile duct dilatation and bile duct wall thickening around the lesion. Five patients (62.5%, 5/8) were followed up. After chemotherapy, the lesions were completely relieved (60.0%), or decreased (40.0%). Conclusion: AIDS-HKS presented as multiple nodular lesions with different imaging features. The combination of different imaging methods was helpful for the imaging diagnosis of AIDS-HKS.

6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(3): 286-292, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38538358

RESUMEN

OBJECTIVE: To investigate the effect of early pulmonary rehabilitation (PR) training on the improvement of respiratory function in patients with acute respiratory distress syndrome (ARDS) after weaning of invasive mechanical ventilation in the intensive care unit (ICU). METHODS: The retrospective cohort research method was used. The clinical information of adult patients with ARDS receiving invasive mechanical ventilation admitted to the ICU of Qingdao Municipal Hospital from January 2019 to March 2023 was collected. The patients were divided into a control group and an observation group according to off-line training program. The control group received traditional training after weaning, and the observation group received the early PR training after weaning. Other treatments and nursing were implemented according to the routine of the ICU. The scores of the short physical performance battery (SPPB) on day 3-day 6 of the weaning training, respiratory muscle strength, level of interleukin-6 (IL-6), number of aspirations of sputum after weaning, length of stay after weaning, rehospitalization rate within 6 months after discharge, and pulmonary function indicators at discharge and 3 months after discharge [peak expiratory flow (PEF), forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC), and vital capacity (VC)] of the two groups of patients were compared. The Kaplan-Meier survival curve was drawn to analyze the cumulative survival rate of patients 6 months after discharge. RESULTS: A total of 50 of which 25 cases received the traditional training after weaning, 25 cases received the early PR training after weaning. There was no significant difference in gender, age, acute physiology and chronic health evaluation II (APACHE II), oxygenation index upon admission, etiological diagnosis of ARDS upon admission, time of invasive ventilation, mode of invasive mechanical ventilation, pulmonary function indicators at discharge, and other baseline data of the two groups. The SPPB questionnaire scores and respiratory muscle strength in both groups were increased gradually with the extended offline training time, the serum level of IL-6 in both groups were descend gradually with the extended offline training time, especially in the observation group [SPPB questionnaire score in the observation group were 7.81±0.33, 8.72±0.53, 9.44±0.31, 10.57±0.50, while in the control group were 7.74±0.68, 8.73±0.37, 8.72±0.40, 9.33±0.26, effect of time: F = 192.532, P = 0.000, effect of intervention: F = 88.561, P = 0.000, interaction effect between intervention and time: F = 24.724, P = 0.000; respiratory muscle strength (mmHg, 1 mmHg≈0.133 kPa) in the observation group were 123.20±24.84, 137.00±26.47, 149.00±24.70, 155.40±29.37, while in the control group were 129.00±20.34, 126.00±24.01, 132.20±25.15, 138.60±36.67, effect of time: F = 5.926, P = 0.001, effect of intervention: F = 5.248, P = 0.031, interaction effect between intervention and time: F = 3.033, P = 0.043; serum level of IL-6 in the observation group were 80.05±6.81, 74.76±9.33, 63.66±10.19, 56.95±4.72, while in the control group were 80.18±7.21, 77.23±9.78, 71.79±10.40, 66.51±6.49, effect of time: F = 53.485, P = 0.000, effect of intervention: F = 22.942, P = 0.000, interaction effect between intervention and time: F = 3.266, P = 0.026]. Compared with the control group, the number of aspirations of sputum after weaning of patients in the observation group significantly decreased (number: 22.46±1.76 vs. 27.31±0.90), the length of ICU stay after weaning significantly became shorter (days: 6.93±0.95 vs. 8.52±2.21), and the rehospitalization rate within 6 months after discharge significantly decreased [20.00% (5/25) vs. 48.00% (12/25)]. There were significant differences. The pulmonary function indicators 3 months after discharge of two groups of patients significantly increased compared with those at discharge and those of the observation group were significantly higher than those of the control group [PEF (L/min): 430.20±95.18 vs. 370.00±108.44, FEV1/FVC ratio: 0.88±0.04 vs. 0.82±0.05, VC (L): 3.22±0.72 vs. 2.74±0.37, all P < 0.05]. The Kaplan-Meier survival curve showed that the cumulative survival rate of patients 6 months after discharge of patients in the observation group was significantly higher than that of patients in the control group [76.9% vs. 45.5%, hazard ratio (HR) = 0.344, P = 0.017]. CONCLUSIONS: Early PR training can significantly improve the respiratory function of patients with ARDS after weaning of invasive mechanical ventilation. Continuous active respiratory training after discharge can improve the respiratory function of patients and effectively decrease mortality.


Asunto(s)
Respiración Artificial , Síndrome de Dificultad Respiratoria , Adulto , Humanos , Respiración Artificial/métodos , Estudios Retrospectivos , Interleucina-6 , Desconexión del Ventilador , Síndrome de Dificultad Respiratoria/terapia , Pronóstico , Volumen de Ventilación Pulmonar , Unidades de Cuidados Intensivos
7.
JMIR Med Educ ; 10: e52711, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38050366

RESUMEN

BACKGROUND: The emergence of the COVID-19 pandemic has posed a significant ethical dilemma in the allocation of scarce, life-saving medical equipment to critically ill patients. It remains uncertain whether medical students are equipped to navigate this complex ethical process. OBJECTIVE: This study aimed to assess the ability and confidence of medical students to apply principles of medical ethics in allocating critical medical devices through the scenario of virtual patients. METHODS: The study recruited third- and fourth-year medical students during clinical rotation. We facilitated interactions between medical students and virtual patients experiencing respiratory failure due to COVID-19 infection. We assessed the students' ability to ethically allocate life-saving resources. Subsequently, we analyzed their written reports using thematic analysis to identify the ethical principles guiding their decision-making. RESULTS: We enrolled a cohort of 67 out of 71 medical students with a mean age of 34 (SD 4.7) years, 60% (n=40) of whom were female students. The principle of justice was cited by 73% (n=49) of students while analyzing this scenario. A majority of them expressed hesitancy in determining which patient should receive life-saving resources, with 46% (n=31) citing the principle of nonmaleficence, 31% (n=21) advocating for a first-come-first-served approach, and 25% (n=17) emphasizing respect for patient autonomy as key influencers in their decisions. Notably, medical students exhibited a lack of confidence in making ethical decisions concerning the distribution of medical resources. A minority, comprising 12% (n=8), proposed the exploration of legal alternatives, while 4% (n=3) suggested medical guidelines and collective decision-making as potential substitutes for individual ethical choices to alleviate the stress associated with personal decision-making. CONCLUSIONS: This study highlights the importance of improving ethical reasoning under time constraints using virtual platforms. More than 70% of medical students identified justice as the predominant principle in allocating limited medical resources to critically ill patients. However, they exhibited a lack of confidence in making ethical determinations and leaned toward principles such as nonmaleficence, patient autonomy, adherence to legal and medical standards, and collective decision-making to mitigate the pressure associated with such decisions.


Asunto(s)
COVID-19 , Estudiantes de Medicina , Humanos , Femenino , Adulto , Masculino , COVID-19/epidemiología , Pandemias , Enfermedad Crítica , Beneficencia
8.
iScience ; 26(10): 107978, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37822512

RESUMEN

Reported herein is a highly efficient dynamic kinetic resolution protocol for the atroposelective synthesis of heterobiaryls with vicinal C-C and N-N diaxes. Atropisomers bearing vicinal diaxes mainly exist in o-triaryls, while that of biaryls is highly challenging in terms of the concerted rotation and deplanarization effects. The combination of C-C biaryl with N-N nonbiaryl delivers a novel class of vicinal-diaxis heterobiaryls. For their atroposelective synthesis, the dynamic kinetic resolution enabled by either quinine-catalyzed allylation or isothiourea-catalyzed acylation has been developed, allowing the preparation of a wide range of vicinal-axis heterobiaryls in good yields with excellent enantioselectivities. Atropisomerization experiments revealed that the C-C bond rotation led to diastereomers, and the N-N bond rotation offered enantiomers. Besides, this protocol could be extended to kinetic resolution by employing substrates with a more hindered axis.

9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(8): 800-806, 2023 Aug.
Artículo en Chino | MEDLINE | ID: mdl-37593856

RESUMEN

OBJECTIVE: To analyze the risk factors related to the prognosis of patients with sepsis in intensive care unit (ICU), construct a nomogram model, and verify its predictive efficacy. METHODS: A retrospective cohort study was conducted using data from Medical Information Mart for Intensive Care-IV 0.4 [MIMIC-IV (version 2.0)]. The information of 6 500 patients with sepsis who meet the diagnostic criteria of Sepsis-3 were collected, including demography characteristics, complications, laboratory indicators within 24 hours after ICU admission, and final outcome. Using a simple random sampling method, the patients were divided into a training set and a validation set at a ratio of 7 : 3. The restricted cubic spline (RCS) was used to explore whether there was a linear relationship between each variable and the prognosis, and the nonlinear variables were truncated into categorical variables. All variables were screened by LASSO regression and included in multivariate Cox regression analysis to analyze the death risk factors in ICU patients with sepsis, and construct a nomograph. The consistency index, calibration curve and receiver operator characteristic curve (ROC curve) were used to evaluate the prediction efficiency of nomogram model. The decision curve analysis (DCA) was used to validate the clinical value of the model and its impact on actual decision-making. RESULTS: Among 6 500 patients with sepsis, 4 551 were in the training set and 1 949 were in the validation set. The 28-day, 90-day and 1-year mortality in the training set were 27.73% (1 262/4 551), 34.76% (1 582/4 551), and 42.98% (1 956/4 551), respectively, those in the validation set were 27.24% (531/1 949), 33.91% (661/1 949), and 42.23% (823/1 949), respectively. Both in training set and the validation set, compared with the final survival patients, the death patients were older, and had higher sequential organ failure assessment (SOFA) score and simplified acute physiology score II (SAPS II), more comorbidities, less urine output, and more use of vasoactive drugs, kidney replacement therapy, and mechanical ventilation. By RCS analysis, the variables with potential nonlinear correlation with the prognosis risk of septic patients were transformed into categorical variable. The variables screened by LASSO regression were enrolled in the multivariate Cox regression model. The results showed that age [hazard ratio (HR) = 1.021, 95% confidence interval (95%CI) was 1.018-1.024], SOFA score (HR = 1.020, 95%CI was 1.000-1.040), SAPS II score > 44 (HR = 1.480, 95%CI was 1.340-1.634), mean arterial pressure (MAP) ≤ 75 mmHg (1 mmHg ≈ 0.133 kPa; HR = 1.120, 95%CI was 1.026-1.222), respiratory rate (RR; HR = 1.044, 95%CI was 1.034-1.055), cerebrovascular disease (HR = 1.620, 95%CI was 1.443-1.818), malignant tumor (HR = 1.604, 95%CI was 1.447-1.778), severe liver disease (HR = 1.330, 95%CI was 1.157-1.530), use of vasoactive drugs within 24 hours (HR = 1.213, 95%CI was 1.101-1.336), arterial partial pressure of oxygen (PaO2; HR = 0.999, 95%CI was 0.998-1.000), blood lactic acid (Lac; HR = 1.066, 95%CI was 1.053-1.079), blood urea nitrogen (BUN) > 8.9 mmol/L (HR = 1.257, 95%CI was 1.144-1.381), total bilirubin (TBil; HR = 1.023, 95%CI was 1.015-1.031), and prothrombin time (PT) > 14.5 s (HR = 1.232, 95%CI was 1.127-1.347) were associated with the death of ICU patients with sepsis (all P < 0.05). Based on the above factors, a nomogram model was constructed, and the model validation results showed that the consistency index was 0.730. The calibration curve showed a good consistency between the predicted results of the nomogram model and observed results in the training and validation sets. ROC curve analysis showed that the area under the ROC curve (AUC) predicted by the nomogram model in the training set and the validation set for 28-day, 90-day and 1-year death risk was 0.771 (95%CI was 0.756-0.786) and 0.761 (95%CI was 0.738-0.784), 0.777 (95%CI was 0.763-0.791) and 0.765 (95%CI was 0.744-0.787), 0.677 (95%CI was 0.648-0.707) and 0.685 (95%CI was 0.641-0.728), respectively. DCA analysis showed that the nomogram model had significant net benefits in predicting 28-day, 90-day, and 1-year death risk, verifying the clinical value of the model and its good impact on actual decision-making. CONCLUSIONS: The death risk factors related to ICU patients with sepsis include age, SOFA score, SAPS II score > 44, MAP ≤ 75 mmHg, RR, cerebrovascular disease, malignant tumors, severe liver disease, use of vasoactive drugs within 24 hours, PaO2, Lac, BUN, TBil, PT > 14.5 s. The nomogram model constructed based on this can predict the death risk of ICU patients with sepsis.


Asunto(s)
Unidades de Cuidados Intensivos , Sepsis , Humanos , Pronóstico , Estudios Retrospectivos , Nomogramas , Sepsis/diagnóstico
10.
BMC Gastroenterol ; 23(1): 285, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37592280

RESUMEN

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a syndrome with high 28- and 90-day mortality rates. Magnetic resonance imaging (MRI) has been widely used to diagnose and evaluate liver disease. Our purpose is to determine the value of the imaging features derived from Gd-DTPA-enhanced MRI for predicting the poor outcome of patients with ACLF and develop a clinically practical radiological score. METHODS: This retrospective study comprised 175 ACLF patients who underwent Gd-DTPA-enhanced abdominal MRI from January 2017 to December 2021. The primary end-point was 90-day mortality. Imaging parameters, such as diffuse hyperintense of the liver on T2WI, patchy enhancement of the liver at the arterial phase, uneven enhancement of the liver at the portal vein phase, gallbladder wall edema, periportal edema, ascites, esophageal and gastric varix, umbilical vein patefac, portal vein thrombosis, and splenomegaly were screened. Cox proportional hazard regression models were used to evaluate prognostic factors and develop a prediction model. The accuracy of the model was evaluated by receiver operating characteristic (ROC) curves. RESULTS: During the follow-up period, 31 of the 175 ACLF patients died within 90 days. In the multivariate analysis, three imaging parameters were independently associated with survival: diffuse hyperintense on T2WI (p = 0.007; HR = 3.53 [1.40-8.89]), patchy enhancement at the arterial phase (p = 0.037; HR = 2.45 [1.06-5.69]), moderate ascites (vs. mild) (p = 0.006; HR = 4.12 [1.49-11.36]), and severe ascites (vs. mild) (p = 0.005; HR = 4.29 [1.57-11.71]). A practical radiological score was proposed, based on the presence of diffuse hyperintense (7 points), patchy enhancement (5 points), and ascites (6, 8, and 8 points for mild, moderate, and severe, respectively). Further analysis showed that a cut-off at 14 points was optimum to distinguish high-risk (score > 14) from the low-risk group (score ≤ 14) for 90-day survival and demonstrated a mean area under the ROC curve of 0.774 in ACLF patients. CONCLUSIONS: Gd-DTPA-enhanced MR imaging features can predict poor outcomes in patients with ACLF, based on which we proposed a clinically practical radiological score allowing stratification of the 90-day survival.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Enfermedades de la Vesícula Biliar , Humanos , Insuficiencia Hepática Crónica Agudizada/diagnóstico por imagen , Ascitis/diagnóstico por imagen , Ascitis/etiología , Gadolinio DTPA , Estudios Retrospectivos , Imagen por Resonancia Magnética , Pronóstico
11.
Eur J Med Chem ; 258: 115596, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37406383

RESUMEN

Hepatic fibrosis poses a significant threat to human health due to excessive extracellular matrix (ECM) deposition leading to liver function damage. Ligand-activated vitamin D receptor (VDR) has been identified as an effective target for hepatic fibrosis, reducing ECM by inhibiting hepatic stellate cell (HSC) activation. Here, a series of novel diphenyl VDR agonists have been rationally designed and synthesized. Among these, compounds 15b, 16i, and 28m showed better transcriptional activity compared to sw-22, which was previously reported to be a potent non-secosteroidal VDR modulator. Moreover, these compounds exhibited outstanding efficacy to inhibit collagen deposition in vitro. In models of CCl4-induced and bile duct ligation-induced hepatic fibrosis, compound 16i showed the most significant therapeutic effect by ultrasound imaging and histological examination. Moreover, 16i was able to repair liver tissue by reducing the expression levels of fibrosis genes and serum liver function indexes without causing hypercalcemia in mice. In conclusion, compound 16i is a potent VDR agonist with significant anti-hepatic fibrosis action both in vitro and in vivo.


Asunto(s)
Hepatopatías , Receptores de Calcitriol , Humanos , Ratones , Animales , Receptores de Calcitriol/agonistas , Cirrosis Hepática/metabolismo , Hígado/metabolismo , Fibrosis
12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(6): 592-597, 2023 Jun.
Artículo en Chino | MEDLINE | ID: mdl-37366124

RESUMEN

OBJECTIVE: To explore the effect of interleukin-17A (IL-17A) on liver and kidney injury and prognosis in septic mice. METHODS: A total of 84 SPF male C57BL/6 mice were randomly divided into sham operation group (Sham group), cecal ligation and puncture (CLP) induced sepsis model group (CLP group), and IL-17A intervention group. IL-17A intervention group were then divided into five subgroups according to the dose of IL-17A (0.25, 0.5, 1, 2, 4 µg). Mice in the IL-17A intervention group were intraperitoneally injected with the corresponding dose of IL-17A 100 µL immediately after surgery. The other groups were intraperitoneally injected with 100 µL phosphate buffer solution (PBS). The survival rate of mice was observed at 7 days, and peripheral blood and liver, kidney and spleen tissues were collected. According to the 7-day survival, another 18 mice were randomly divided into Sham group, CLP group, and 1 µg IL-17A intervention group. Peripheral blood samples were collected at 12 hours and 24 hours after CLP, and the mice were sacrificed to obtain liver, kidney, and spleen tissues. The behavior and abdominal cavity of each group were observed. The levels of peripheral blood liver and kidney function indexes and inflammatory factors were detected. The histopathological changes of liver and kidney were observed under light microscope. The peripheral blood and spleen tissues were inoculated in the medium, the number of bacterial colonies was calculated, and the bacterial migration of each group was evaluated in vitro. RESULTS: Except for the Sham group, the 7-day survival rate of mice in the 1 µg IL-17A intervention group was the highest (75.0%), so this condition was selected as the intervention condition for the subsequent study. Compared with Sham group, the liver and kidney functions of CLP group were significantly damaged at each time point after operation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (SCr) reached the peak at 24 hours after operation, and the liver and kidney pathological scores reached the peak at 7 days after operation, the levels of inflammatory cytokines interleukin (IL-17A, IL-6, IL-10) reached the peak at 12 hours after operation, and tumor necrosis factor-α (TNF-α) reached the peak at 24 hours after operation. In addition, a large number of bacteria proliferated in the peripheral blood and spleen, which reached the peak on day 7. Compared with the CLP group, exogenous administration of 1 µg IL-17A significantly delayed the rising trend of each index in the early stage of sepsis [24-hour ALT (U/L): 166.95±5.20 vs. 271.30±6.11, 24-hour AST (U/L): 599.42±7.25 vs. 1 013.27±3.37, 24-hour BUN (mg/L): 815.4±26.3 vs. 1 191.2±39.4, 24-hour SCr (µmol/L): 29.34±0.87 vs. 60.75±3.83, 7-day liver pathological score: 2.50 (2.00, 3.00) vs. 9.00 (8.50, 9.00), 7-day kidney pathological score: 1.00 (1.00, 2.00) vs. 5.00 (4.50, 5.00), 12-hour IL-17A (ng/L): 105.21±0.31 vs. 111.28±1.37, 12-hour IL-6 (ng/L): 83.22±1.01 vs. 108.88±0.99, 12-hour IL-10 (ng/L): 731.54±3.04 vs. 790.25±2.54, 24-hour TNF-α (µg/L): 454.67±0.66 vs. 576.18±0.76, 7-day peripheral blood colony count (CFU/mL): 600 (400, 600) vs. 4 200 (4 200, 4 300), 7-day spleen tissue colony count (CFU/g): 4 600 (4 400, 4 600) vs. 23 400 (23 200, 23 500), all P < 0.05]. CONCLUSIONS: Appropriate dose (1 µg) of exogenous IL-17A can reduce the lethal inflammatory response induced by CLP and improve the ability of bacterial clearance, thereby alleviating liver and kidney injury and improving the 7-day survival rate of septic mice.


Asunto(s)
Interleucina-17 , Sepsis , Animales , Masculino , Ratones , Interleucina-10 , Interleucina-17/farmacología , Interleucina-6 , Riñón/fisiopatología , Hígado/fisiopatología , Ratones Endogámicos C57BL , Pronóstico , Factor de Necrosis Tumoral alfa
13.
Entropy (Basel) ; 25(3)2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36981403

RESUMEN

Physically implemented neural networks are subject to external perturbations and internal variations. Existing works focus on the adversarial attacks but seldom consider attack on the network structure and the corresponding recovery method. Inspired by the biological neural compensation mechanism and the neuromodulation technique in clinical practice, we propose a novel framework of reviving attacked reservoir computers, consisting of several strategies direct at different types of attacks on structure by adjusting only a minor fraction of edges in the reservoir. Numerical experiments demonstrate the efficacy and broad applicability of the framework and reveal inspiring insights into the mechanisms. This work provides a vehicle to improve the robustness of reservoir computers and can be generalized to broader types of neural networks.

14.
Curr Med Imaging ; 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38254291

RESUMEN

BACKGROUND: Chronic liver disease (CLD) will affect the enhancement of hepatic parenchyma and portal vein on abdominal-enhanced MRI. OBJECTIVE: To investigate the difference in liver parenchyma and portal vein enhancement in patients with CLD of different liver function grades between Gd- EOB-DTPA and Gd-DPTA in the portal venous phase (PVP). METHODS: This retrospective study included 218 patients with CLD who had undergone abdominal enhanced MRI from January 2019 to June 2020. Patients with various degrees of liver dysfunction were identified with Child-Turcotte-Pugh and albumin-bilirubin grade. Two readers measured the precontrast and PVP signal intensities of liver parenchyma, portal vein, spleen, and psoas muscle. Relative liver enhancement, liver-to-spleen contrast index, portal vein image contrast, and portal vein-to-liver contrast were calculated. RESULTS: The relative enhancement of liver parenchyma was significantly lower for the Gd-EOB-DTPA group in any degree of liver function than the Gd- DTPA group in the PVP. The Gd-EOB-DTPA group showed significantly lower portal vein-to-liver contrast in the overall study population, CTP class B, and ALBI grade 2 patients compared to the group of Gd-DTPA at PVP. No significant difference was noted in the portal vein image contrast between the two contrast agents, regardless of CTP and ALBI grading. CONCLUSION: In CLD patients, Gd-EOB-DTPA yielded lower liver parenchymal enhancement and similar portal vein image contrast compared to Gd-DTPA in the PVP. Portal vein-to-liver contrast in the Gd-EOB-DTPA group was lower in the CTP class B and ALBI grade 2 subgroups compared to the Gd- DTPA group.

15.
Medicine (Baltimore) ; 101(45): e31123, 2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36397319

RESUMEN

BACKGROUND: Elevated triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C) are recognized as essential and independent hazard factors for total death and major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD). However, whether the increased TG/HDL-C forecasted the prognosis of CHD is still unknown. Therefore, we performed a meta-analysis to investigate the relationship between the elevated TG/HDL-C ratio and poor prognosis of CHD. METHODS: A systematic literature search was conducted in PubMed, Web of Science, EMBASE, and The Cochrane Library, until August 30, 2021. Prospective observational studies regarding the association between TG/HDL-C and long-term mortality/MACEs in CHD patients were included. RESULTS: In total, 6 independent prospective studies of 10,222 participants with CHD were enrolled in the systematic and meta-analysis. Our outcomes of the meta-analysis indicated that the elevated TG/HDL-C group had a significantly increased risk of long-term all-cause mortality (hazard ratio [HR] = 2.92, 95% confidence interval [CI]: 1.75-4.86, P < .05) and long-term MACEs (HR = 1.56, 95%CI 1.11-2.18, P < .05). CONCLUSION: In patients with CHD, the present study showed that the high TG/HDL-C was associated with increased risk of long-term all-cause mortality and MACE.


Asunto(s)
Enfermedad Coronaria , Hipertrigliceridemia , Humanos , HDL-Colesterol , Triglicéridos , Estudios Prospectivos , Factores de Riesgo , Hipertrigliceridemia/complicaciones , Colesterol , Pronóstico , Estudios Observacionales como Asunto
16.
Infect Drug Resist ; 15: 6029-6037, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36267264

RESUMEN

Purpose: To retrospectively analyse the CT imaging during the long-term follow-up of COVID-19 patients after discharge. Patients and Methods: A total of 122 patients entered the study group. All patients underwent CT examinations. The CT images, which included distribution and imaging signs, were evaluated by two chest radiologists. Laboratory examinations included routine blood work, biochemical testing, and SARS-CoV-2 antibody screening. Statistical methods include chi-square, Fisher's exact test, one-way analysis of variance, rank sum test and logistic regression by SPSS 17.0. Results: There were 22 (18.0%) patients in the mild group, 74 (60.7%) patients in the moderate group, and 26 (21.3%) patients in the severe-critical group. The median follow-up interval was 405 days (378.0 days, 462.8 days). Only monocytes, prothrombin activity, and γ-glutamyltransferase showed significant differences among the three groups. We found that the more severe the patient's condition, the more SARS-CoV-2 IgG antibodies existed. Only 11 patients (11.0%) showed residual lesions on CT. The CT manifestations included irregular linear opacities in nine cases (9.0%), reticular patterns in six cases (6.0%), and GGOs in five cases (5.0%). Conclusion: The proportion of residual lesions on CT in COVID-19 patients was significantly reduced after long-term follow-up. The patients' age and disease conditions were positively correlated with residual lesions.

17.
BMC Med Imaging ; 22(1): 185, 2022 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-36309647

RESUMEN

BACKGROUND: Establish a CT-based diagnostic radiomic model for AIDS complicated with pulmonary cryptococcosis and evaluate the diagnostic efficacy of this model. METHODS: This retrospective study enrolled 98 AIDS patients with pulmonary cryptococcosis and 103 AIDS patients with other infections or neoplastic lesions, comprising a total of 699 lesions. Patients were randomly divided into a training group and test group at a ratio of 2.75:1. Features from all lesions, cavity lesions and solid nodule lesions were extracted, and two kinds of radiomic models (6 types) were established. ROC curves were drawn, and the sensitivity and specificity were calculated to compare the SVM model and LR model, radiologists' empirical diagnoses and the combination of these empirical diagnoses with the radiomic model. RESULTS: The AUCs of senior radiologist for all lesions and cavity lesions were lower than those of the SVM and LR models. The diagnostic efficacy of primary radiologist was lower than that of both of the other model types. The diagnostic efficacy of the LR model was relatively stable, with the highest diagnostic efficiency of the 3 model/radiologist groups. The AUCs of intermediate radiologist in combination with the LR radiomic model for all lesions, nodular lesions and cavity lesions were 0.88, 0.84, and 0.9, respectively, which were the highest among all models and radiologists. CONCLUSIONS: The CT-based radiomic LR model of AIDS-associated pulmonary cryptococcosis exhibits good diagnostic performance, which was similar to that of senior radiologists and higher than that of the primary radiologist. With the help of a radiomic model, radiologists can achieve improved diagnostic accuracy compared to that when only an empirical diagnosis is used.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Criptococosis , Humanos , Estudios Retrospectivos , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/diagnóstico por imagen , Curva ROC , Tomografía Computarizada por Rayos X , Criptococosis/diagnóstico por imagen
18.
Medicine (Baltimore) ; 101(33): e30060, 2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-35984191

RESUMEN

INTRODUCTION: Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality. PATIENT CONCERNS: A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC). DIAGNOSIS: The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results. INTERVENTIONS: The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines. OUTCOMES: Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red. CONCLUSION: This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis.


Asunto(s)
Colitis Ulcerosa , Síndrome de Hipersensibilidad a Medicamentos , Hipersensibilidad a las Drogas , Exantema , Colitis Ulcerosa/complicaciones , Hipersensibilidad a las Drogas/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Exantema/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Sulfasalazina/efectos adversos
19.
Front Endocrinol (Lausanne) ; 13: 917386, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35909537

RESUMEN

Gestational diabetes mellitus (GDM), the most common medical pregnancy complication, has become a growing problem. More and more studies have shown that microRNAs are closely related to metabolic processes. The purpose of this paper is to investigate the role of up-regulation of miR-199a-5p expression in GDM. We found that miR-199a-5p was significantly up-regulated in the placenta of GDM patients compared with normal pregnant women, and expressed in placental villi. miR-199a-5p can regulate the glucose pathway by inhibiting the expression of methyl CpG-binding protein 2 (MeCP2) and down-regulating canonical transient receptor potential 3 (Trpc3). This suggests that miR-199a-5p may regulate the glucose pathway by regulating methylation levels, leading to the occurrence of GDM.


Asunto(s)
Diabetes Gestacional , MicroARNs , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Femenino , Glucosa/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Placenta/metabolismo , Embarazo , Regulación hacia Arriba
20.
Regen Biomater ; 9: rbac016, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35480860

RESUMEN

Endometrial injury can cause intrauterine adhesions (IUA) and induce the formation of endometrial fibrosis, leading to infertility and miscarriage. At present, there is no effective treatment method for severe IUA and uterine basal injury with adhesion area larger than one-third of the uterus. In this study, we prepared FGF1 silk sericin hydrogel material (FGF1-SS hydrogel) to treat endometrial injury and prevent endometrial fibrosis. Compared with the silk sericin hydrogel material (WT-SS hydrogel), FGF1-SS hydrogel significantly promotes the cell migration and infiltration ability of endometrial stromal cells (ESCs). More importantly, FGF1-SS hydrogel can release FGF1 stably for a long time and inhibit the ESCs injury model forms fibrosis through the TGF-ß/Smad pathway. In the IUA rat model, FGF1-SS hydrogel treatment effectively restored the number of uterine glands and uterine wall thickness in rats, with a fertility rate of 65.1% ± 6.4%. The results show that FGF1-SS hydrogel is expected to be a candidate to prevent IUA.

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