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[Objective]To explore residents'science popularization status of traditional Chinese medicine(TCM)and its influential factors,and provid scientific suggestions for the formulation of strategies and methods of TCM science popularization,taking Sanfu herbal patch(SHP)as an example.[Methods]Online questionnaires and Logistic regression analysis were applied to study residents'cognition,behavior and willingness on SHP and its influential factors,and explor the effective strategies and methods of TCM science popularization.[Results]Residents'cognitive accuracy rates of SHP's efficacy in treating diseases were 22.9％for bronchitis or chronic obstructive pulmonary disease,21.4％for rhinitis,19.3％for health care and immunity enhancement,and those of treatment methods were 35.0％for the reimbursement by medical insurance and 20.3％for the number of medication per course.Only 7.8％of residents experienced the treatment.Ways of acquiring SHP knowledge were few,namely,personal communication(26.6％)and internet(22.6％).Patients with underlying diseases,with odds ratio(OR)of 2.44(P＜0.05),were the most important factor promoting the cognitive accuracy of diseases that can be treated with SHP.Female(OR=1.70,P＜0.01)and insured residents(OR=2.41,P＜0.01)were factors that promoted the cognitive accuracy of treatment methods.The demand rate of knowledge was 71.7％,and that of the elderly was 100％;and approval rates of SHP science popularization at home and abroad were 78.2％and 80.0％.[Conclusion]Residents'science knowledge and application level of SHP were low,but their passion to try,learn and communicate it was very high.Therefore,it was suggested to increase the micro education of specific TCM treatments,take female,patients with basic diseases,insured residents and the elderly as starting points,expanding the audience,create diversified paths,and improve the precise implementation of science popularization strategies,so as to improve the health literacy of residents and promote the development of healthy China.
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Myocardial fibrosis （MF） is a prevalent pathological process in a spectrum of cardiac conditions， including myocardial infarction， hypertensive heart disease， and dilated cardiomyopathy. It is marked by an overabundance of extracellular matrix deposition， diminished myocardial compliance， and impaired cardiac function， which can lead to arrhythmias and sudden cardiac death. The current therapeutic approach primarily aims to suppress the progression of fibrosis， yet the therapeutic outcomes are poor. The pathogenesis of MF involves multiple signaling pathways， including the transforming growth factor-beta （TGF-β）/Smads signaling pathway， nuclear factor-kappa B （NF-κB） signaling pathway， phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， and mitogen-activated protein kinase （MAPK） signaling pathway. Traditional Chinese medicine （TCM） boasts a rich history in the treatment of cardiovascular diseases， offering distinctive benefits such as minimal side effects and high safety， and it has demonstrated promising therapeutic effects in the treatment of MF. In recent years， research has turned its attention to the application of TCM in modulating the signaling pathways associated with MF. It has been demonstrated that TCM can modulate the MF-related signaling pathways to exert anti-inflammatory effects， regulate cellular autophagy， cell proliferation， and apoptosis， reduce myocardial oxidative stress and damage， and inhibit the activation of fibroblasts and collagen synthesis， thereby exhibiting the potential to mitigate or even reverse the progression of MF. Experimental research and clinical observations indicate that TCM formulas such as Yixin Futing decoction， Luhong prescription， Zhilong Huoxue Tongyu capsules， and Kangjian Yixin prescription can effectively ameliorate MF and enhance cardiac function through the multi-component regulation of multiple cellular pathways. Specific TCM constituents， including isoliquiritigenin and astragaloside， have been shown to inhibit the expression of TGF-β1， thereby disrupting the Smad signaling pathway. Compounds like glycyrrhizic acid and allicin can suppress the NF-κB signaling pathway and curtail collagen synthesis in myocardial cells， and forsythoside can activate the PI3K/Akt signaling pathway， contributing to its anti-fibrotic effects.
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ObjectiveTo investigate the current status of cognition and attitude towards hospice care among medical staff in Liaocheng，analyze the related influencing factors，and to provide reference for further development of hospice care services. MethodsUsing the method of convenient sampling，404 medical staff from all levels of hospitals in Liaocheng were selected as the research subjects from January to June 2022 to conduct a questionnaire survey on the cognition and attitude towards hospice care.Statistical methods were used to analyze the related influencing factors. ResultsThe knowledge score of hospice care among medical staff in Liaocheng was （13.02 ± 4.10），with an average score rate of 65.10%.The score of attitude was （38.67 ± 5.64），with an average score rate of 64.50%.Age （41~50 years old），having received education and training，treated or cared for patients in the middle and late stages，and understanding ethics and morality，as well as cultural customs were significantly positively correlated with knowledge scores.Age （> 50 years old），professional title （deputy senior professional title），position （medical treatment），and experience in treating or caring for patients in the middle and late stages were positively related to attitude scores. ConclusionThe cognition and attitude towards hospice care among medical staff in Liaocheng were at a moderate level.Strengthening the construction of a standardized hospice care system is helpful to improve the cognition and attitude level towards hospice care among medical staff.
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BACKGROUND:Subepithelial connective tissue grafts are generally considered as the gold standard for soft tissue augmentation.However,it needs a second surgical site,which will prolong the surgical time and increase patients'pain. OBJECTIVE:To compare the histological and thickness changes of attached gingiva following grafting with different soft tissue substitutes in the labial region of the cuspids. METHODS:In three Beagle dogs,attached gingival augmentation was performed with double-layer allogeneic acellular dermal matrix membrane(AADM),bovine-derived acellular dermal matrices(BADM)combined with concentrated growth factor membrane or BADM combined with collagen sponge.Thickness of attached gingiva was measured before augmentation,and 1,2,3,and 4 months after augmentation.Histological analyses were performed after 4 months. RESULTS AND CONCLUSION:The mean values of attached gingival thickness and attached gingival thickness augmentation were higher in the double-layer AADM group than in the other two groups(all P<0.05)from the 1st to 4th month after surgery.At 1 month after surgery,the attached gingival thickness of the three groups increased significantly and then decreased.At 3 months after surgery,the BADM combined with collagen sponge group and the BADM combined with concentrated growth factor membrane group showed no significant difference in the attached gingival thickness of the graft area compared with that before surgery(P>0.05).At 4 months after surgery,the mean value of attached gingival thickness in the double-layer AADM group was still significantly increased compared with that before surgery(P<0.05).The value of attached gingival thickness was highest in the double-layer AADM group,followed by the BADM combined with collagen sponge group,and the lowest in the BADM combined with concentrated growth factor membrane group at 1-4 months after surgery.Histological analyses revealed that AADM was well integrated with the host gingival tissue,and new fibrous connective tissue and fibroblasts grew into the AADM.But the grafts in the other two groups were absorbed and the augmentation area was remodeled into a structure consistent with the surrounding host tissue.To conclude,AADM is superior to BADM combined with concentrated growth factor and BADM combined with collagen sponge with regard to gingival augmentation.
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Objective:To assess the value of S-Detect and contrast-enhanced ultrasound (CEUS) in the differential diagnosis of Breast Imaging Reporting and Data System(BI-RADS) 4 breast lesions.Methods:A total of 104 breast lesions in 100 patients diagnosed as BI-RADS category 4 by conventional ultrasound were prospectively enrolled, and all of them were received S-Detect and CEUS examination at the same time. Taking pathology as the gold standard, ROC curve was constructed to compare the diagnostic efficacy of conventional ultrasound, S-Detect, CEUS and their combination.Results:Among the 104 BI-RADS category 4 breast lesions, 63 were benign and 41 were malignant. The sensitivities of conventional ultrasound, S-Detect, CEUS and S-Detect combined with CEUS were 73.17%, 87.80%, 87.80%, 90.24%; the specificities were 57.14%, 60.32%, 68.25%, 77.78%; the positive predictive values were 52.63%, 59.02%, 64.29% and 72.55%; the negative predictive values were 76.60%, 88.37%, 89.59% and 92.45%; the accuracies were 63.46%, 71.15%, 75.96% and 82.69%; and the areas under the ROC curve (AUC) were 0.652, 0.741, 0.780 and 0.840. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of S-Detect and CEUS diagnosis were improved compared with conventional ultrasound. The AUC of combined diagnosis was higher than that of S-Detect, CEUS alone, and the differences were statistically significant(all P<0.05). The AUC of CEUS was higher than that of conventional ultrasound, and the difference was statistically significant ( P<0.05). There were no significant differences in AUC between any two of other groups (all P>0.05). Conclusions:The combined application of S-Detect and CEUS could achieve complementary advantages, which is of great significance for the differential diagnosis of benign and malignant in BI-RADS 4 breast lesions.
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ObjectiveTo explore the application value of CT pulmonary angiography (CTPA) in assessing the severity of acute pulmonary embolism (APE) and right heart function in rehabilitation patients. MethodsFrom January, 2013 to January, 2020, 133 inpatients (94 positive and 39 negative) who underwent CTPA examination in Beijing Bo'ai Hospital were involved. Positive patients were further divided into mild, moderate and severe groups based on the pulmonary artery obstruction index (PAOI). The clinical parameters and right heart function indicators were compared. Spearman correlation analysis was used to analyze the correlation between PAOI, and clinical parameters and right heart function indicators, and Logistic regression analysis was used to predict the risk factors of APE. ResultsThere was significant difference in lower extremity venous thrombosis, D-dimer, oxygen partial pressure, PAOI and left process of interventricular septum among four groups (H ≥ 12.350, P < 0.01). PAOI was moderately positively correlated with D-dimer (r = 0.443, P < 0.001) and left process of interventricular septum (r = 0.520, P < 0.001), and was weakly positively correlated with lower extremity venous thrombosis (r = 0.399, P < 0.001), left pulmonary artery diameter (r = 0.213, P = 0.014) and inferior vena cava regurgitation (r = 0.229, P = 0.008). Lower extremity venous thrombosis (OR = 7.708, P < 0.001) and left process of interventricular septum (OR = 3.641, P = 0.008) were independent risk factors for the onset of APE. The combination of the two indicators was effective for diagnosis of APE, and AUC was 0.795 (95% CI 0.715 to 0.874). ConclusionCTPA may be applied to evaluate the severity of APE and right heart function in rehabilitation patients.
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BACKGROUND@#Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment.@*METHODS@#Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature.@*RESULTS@#There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib.@*CONCLUSIONS@#At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
Sujets)
Animaux , Humains , Souris , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Tumeurs du poumon/génétique , Mutation , Inhibiteurs de protéines kinases/usage thérapeutique , Protéines proto-oncogènes B-raf/génétiqueRésumé
Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.
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Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.
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Objective:To develop a nomogram model for screening of type 2 diabetes mellitus in a community population.Methods:From October to December, 2020, 6 028 community residents who participated in the " national health physical examination" in Karamay community with complete physical examination data and met the inclusion and exclusion criteria were selected. The physical examination data included medical history, physical examination, laboratory, and ultrasound reports. Random segmentation sampling was used to divide the population into modeling and validation cohorts, and LASSO regression analysis was used to screen for independent factors associated with diabetes diagnosis. The independent influencing factors were furthor incorporated into the multi-factor logistic regression, and the RMS software package was used to construct the column chart. The area under receiver operating characteristic(ROC) curve was used to measure the differentiation of the model. The calibration curve can directly reflect the calibration degree of the model.Results:In the modeling group, multivariate logistic regression analysis showed that age, gender(female), history of hypertension, history of hyperlipidemia, HbA 1C, urinary microalbumin, homeostasis model assessment for insulin resistance, and triglycerides and glucose index were independently associated with diabetes. OR were 1.053(95% CI 1.038-1.069), 0.681(95% CI 0.512-0.906), 1.802(95% CI 1.227-2.626), 1.789(95% CI 1.303-2.448), 10.973(95% CI 8.318-14.745), 1.002(95% CI 1.001-1.004), 2.914(95% CI 2.248-3.799), and 2.673(95% CI 2.03-3.536), respectively. The areas under ROC curves of the training set and the validation set were 0.945 and 0.955, respectively. The optimal critical value in the ROC curve was 0.178(sensitivity 0.930, specificity 0.839) in the training set and 0.201(sensitivity 0.945, specificity 0.848) in the validation set. Conclusion:The screening model of type 2 diabetes developed in this study has good accuracy, which can be used as a screening tool for high-risk population of type 2 diabetes.
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Objective:To stimulate innovation vitality, the government promulgated the Pilot Implementation Plan for Granting Scientific and Technological Achievements Ownership or Long- term Use Right to Scientific Research Investigators. As one of the 40 pilot institutions, Beijing JiShuiTan Hospital attached great attention to it and, through the exploration and practice of pilot work, combined with the transformation of medical institutions' achievements Status quo, summarized the experiences of job scientific and technological achievements empowerment. Methods:Explored the mechanism and mode to empower researchers with the ownership or long-term right of service invention according to the policy review and case studies.Results:Developed hospital-level empowerment reform program and related supporting documents, Beijing JiShuiTan Hospital has completed the first empowerment work in Beijing.Conclusions:The reform of empowering scientific and technological achievements gives a new pathway to transform scientific and technological achievements in medical institutions, which will promote the transformation process of service invention-creation.
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Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of malignant endometrial lesions.Methods:A total of 142 patients with endometrial lesions who underwent contrast-enhanced ultrasound examination in Beijing Tiantan Hospital, Capital Medical University from January 2019 to September 2021 were selected. The endometrial lesions were divided into benign group (including endometrial hyperplasia and endometrial polyps) and malignant group (endometrial cancer) according to the pathological results of surgery, and the differences of contrast enhancement patterns between benign group and malignant group were compared. The sensitivity, specificity of CEUS in the diagnosis of endometrial cancer were calculated, and the Kappa value was calculated with the initial enhancement time earlier than or equal to the muscularity or the peak time earlier than the muscularity as the diagnostic index for the diagnosis of endometrial malignant lesions. The sensitivity, specificity, and Kappa value of CEUS in the diagnosis of endometrial cancer and endometrial cancer with thickness ≥10 mm were calculated.Results:A total of 108 patients underwent surgery with clear pathological results, including 66 patients in the benign lesion group and 42 patients in the malignant lesion group. The thickness of malignant lesions was significantly larger than that of benign lesions, and the difference was statistically significant( t=4.039, P<0.05), but there was no significant difference of hemodynamic parameters between the two groups ( P>0.05). The initial enhancement time, peak time and peak intensity of benign lesions were significantly different from those of malignant lesions(all P<0.05). The sensitivity, specificity, and Kappa value of CEUS in the diagnosis of endometrial cancer were 64.3%, 100% and 0.668, respectively. The sensitivity, specificity and Kappa value of CEUS in the diagnosis of endometrial carcinoma with lesion thickness ≥10 mm were 75.0%, 100% and 0.795, respectively. Conclusions:For the diagnosis of endometrial lesions, especially the malignant endometrial lesions with thickness and diameter greater than or equal to 10mm, there is a high diagnostic coincidence rate between CEUS and pathological diagnosis, and endometrial malignant lesions have more specific CEUS manifestations.
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Objective@#To create a model to predict nosocomial infections in emergency intensive care units (EICU), so as to provide insights into early identification and interventions among patients with nosocomial infections. @*Methods@#All nosocomial infections were collected from patients hospitalized in the EICU of a large tertiary hospital from 2017 to 2020. The 2017-2019 data were selected as the training set to create a logistic regression model, and the fitting effectiveness of the predictive model was evaluated using Hosmer-Lemeshow test. The 2020 data were selected as the test set to evaluate the external validation of the predictive model. In addition, the value of the model for prediction of nosocomial infections was examined using the receiver operating characteristic (ROC) curve analysis. @*Results @#Totally 1 546 inpatients in EICU were enrolled, and the prevalence of nosocomial infections was 7.18%. Multivariable logistic regression analysis identified hospital stay duration of >7 days (OR=21.845, 95%CI: 7.901-60.398), use of ventilators (OR=3.405, 95%CI: 1.335-8.682), and surgery (OR=1.854, 95%CI: 1.121-3.064) as risk factors of nosocomial infections. The predictive model was p=ey/(1+ey), y=-6.105+(3.084×duration of hospital stay)+(1.225×use of ventilators)+(0.617×surgery). The area under ROC curve was 0.806 (95%CI: 0.774-0.838) for the training set and 0.723 (95%CI: 0.623-0.823) for the test set, and if the 0.065 cut-off of the predictive model created by the training set was included in the test set, the predictive value yield a 0.739 sensitivity and 0.642 specificity for prediction of nosocomial infections among patients hospitalized in EICU. @*Conclusion@#The created predictive model for nosocomial infections among patients hospitalized in EICU presents a high accuracy, which shows a satisfactory predictive value for high-risk nosocomial infections.
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Objective:To study the optimal pain control goal for preventing delirium in critical patients.Methods:A prospective cohort study were conducted. The patients admitted to general departments and transferred to the intensive care unit (ICU) due to critical illness in the First People's Hospital of Changde from January 2017 to November 2019 were enrolled. The General data of the patients were collected within 48 hours after admission. All patients admitted to the ICU were evaluated for pain level using the critical care pain observation tool (CPOT) every 8 hours by nurses, and confusion assessment method of ICU (CAM-ICU) was used to screen delirium patient every 8 hours by the leader of nursing team without knowing the pain level of the patients, until the subjects were transferred out of ICU. The receiver operating characteristic (ROC) curve was drawn, the area under ROC curve (AUC) and the optimal threshold were analyzed with delirium as the reference standard; according to the optimal threshold, multivariate Logistic regression analysis was used to evaluate the correlation between CPOT score and delirium.Results:During the study period, 575 patients were admitted to the participating departments and passed the preliminary screening according to the inclusion and exclusion criteria. During the study period, 34 patients were excluded due to incomplete data. Finally, a total of 541 patients were enrolled in the analysis, including 149 patients in delirium group and 392 patients in non-delirium group. There was no significant difference in gender, age, source of patients, education level, smoking history, drinking history, family mental history, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score or other general information between the two groups. There were 10.1% (15/149) of patients in the delirium group used opioids, which was significantly higher than 4.3% (17/392) in the non-delirium group, and the difference was statistically significant ( P < 0.05). The CPOT score in the delirium group was significantly higher than that in the non-delirium group (4.24±1.78 vs. 2.75±1.95, P < 0.01). The patients were subdivided into young group (< 40 years old), middle-aged group (40-65 years old) and old group (> 65 years old) according to age. The analysis results were consistent with the overall analysis results. ROC curve analysis showed that the AUC of CPOT score predicting delirium was 0.719; when the best threshold value of CPOT score was 2.5, the sensitivity was 91.3%, the specificity was 49.0%, the positive predictive value was 40.5% and the negative predictive value was 93.7%. Multivariate Logistic regression analysis showed that the risk of delirium in ICU patients with CPOT score ≥ 3 was 10.043 times higher than that in patients with CPOT score < 3 [odds ratio ( OR) = 10.043, 95% confidence interval (95% CI) was 5.498-18.345, P < 0.001]. When the gender, age, APACHEⅡ score, smoking history, drinking history, opioids usage were adjusted, the risk of delirium in patients with CPOT score ≥ 3 was 10.719 times higher than that in patients with CPOT score < 3 ( OR = 10.719, 95% CI was 5.689-20.196, P < 0.001). Conclusion:The best pain control goal for preventing the occurrence of delirium in ICU patients is a CPOT score of 3 or less.
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Objective:To explore the role of receptor-interaction protein 3 (RIP3) in regulating the infiltration of monocytes/macrophages into the liver in autoimmune hepatitis (AIH).Methods:From January to June in 2018, at Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, 10 AIH patients who underwent liver biopsy were enrolled, and at the same time, 5 age and gender matched individuals with normal liver function and hepatic cyst were selected as control. The infiltration of monocytes/macrophages in the liver tissues was observed by immunofluorescence detection in the patients with AIH and controls. Raw264.7 macrophages were divided into control group, lipopolysaccharide group and lipopolysaccharide+ RIP3 inhibitor GSK872 (GSK872) group. The expression of RIP3, mixed lineage kinase domain like pseudokinase ( MLKL), tumor necrosis factor ( TNF)- α, interleukin ( IL)-6, IL-1 β, nod-like receptor protein 3 ( NLRP3), CC motif chemokine ligand ( CCL)2 and CCL5 at mRNA levels were detected by quantitative polymerase chain reaction (qPCR). Raw264.7 macrophages were also divided into control group, lipopolysaccharide group and lipopolysaccharide + dexamethasone group. The relative expression of TNF- α, NLRP3, RIP3 and MLKL at mRNA level in macrophage were detected by qPCR. Twenty-four 6-week-old female C57BL/6 mice were chosen to establish AIH mice model and were randomly divided into control group, concanavalin A (ConA) group, ConA+ dexamethasone group and ConA+ GSK872 group (6 mice in each group). After the mice were executed, the peripheral blood and liver tissues were collected. The histopathology of mice liver were observed and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The expression of CCL2 and CC motif chemokine receptor 2 ( CCR2) at mRNA level were detected by qPCR. The proportion of macrophages in mice livers were analyzed by flow cytometry. The independent sample t test and one-way analysis of variance were performed for statistical analysis. Results:The percentages of CD68 positive macrophages and MAC387 positive infiltrated mononuclear macrophages in livers of AIH patients were both higher than those of controls ((0.84±0.21)% vs. (0.09±0.03)%, (0.79±0.13)% vs. (0.03±0.01)%), and the differences were statistically significant ( t=3.00 and 4.84; all P<0.05). The expression of RIP3, MLKL, TNF- α, IL-6, IL-1 β, NLRP3, CCL2 and CCL5 at mRNA level of lipopolysaccharide group were all higher than those of control group and lipopolysaccharide+ GSK872 group (1.64±0.16 vs. 1.07±0.07 and 0.63±0.11; 10.45±1.37 vs. 1.10±0.33 and 1.51±0.63; 5.43±0.59 vs. 0.94±0.06 and 2.59±0.45; 204.20±30.73 vs. 1.26 ±0.19 and 111.40±11.62; 20 848.00±362.00 vs. 1.09 ±0.26 and 10 940.00±566.60; 7.47±1.17 vs. 1.09±0.09 and 3.79±0.89; 68.03±5.15 vs. 1.14±0.19 and 14.09±2.62; 5 935.12±96.20 vs. 1.43±0.46 and 673.50±49.10), and the differences were all statistically significant ( t=3.11, 5.21, 6.65, 6.55, 7.57, 3.96, 6.60, 3.06, 8.83, 4.08, 5.46, 2.56, 12.97, 10.16, 25.34 and 14.99; all P<0.05). The expression of TNF- α, NLRP3, RIP3 and MLKL at mRNA level of lipopolysaccharide group were all higher than those of control group and lipopolysaccharide+ dexamethasone group (8.85±1.43 vs. 1.44±0.43 and 3.63±0.63; 6.42±0.86 vs. 0.99±0.12 and 2.07±0.17; 1.72±0.21 vs. 0.93±0.09 and 0.43±0.07; 6.87±0.85 vs. 1.62±0.31 and 1.41±0.29), and the differences were all statistically significant ( t=4.95, 3.33, 6.24, 4.95, 3.04, 5.11, 5.77 and 6.07, all P<0.05). The mice liver of ConA group showed obviously inflammatory cells infiltration and hepatocytes necrosis. The serum ALT and AST levels of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group ((2 569.00±45.44) U/L vs. (49.38±9.07), (103.00±14.07) and (759.30±34.99) U/L; (3 335.00±88.79) U/L vs. (108.50±18.10), (460.00±97.40) and (1 573.85±36.06) U/L), the serum ALT and AST levels of ConA+ dexamethasone group were both lower than those of ConA+ GSK872 group, and the differences were all statistically significant ( t=5.54, 5.42, 3.90, 4.63, 4.16, 3.79, 6.70 and 2.71; all P<0.05). The expression of CCL2 and CCR2 at mRNA levels in mice liver of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group (92.64±10.57 vs. 0.78±0.15, 5.64±1.00 and 9.47±2.06; 5.73±0.39 vs. 0.98±0.22, 2.18±0.22 and 2.98±0.33), and the differences were all statistically significant ( t=7.66, 7.24, 5.87, 8.71, 8.58 and 5.45; all P <0.01). The proportion of CD45 + CD11b + F4/80 + total macrophages and CD45 + CD11b hiF4/80 lo infiltrated macrophages in mice livers of ConA group were both higher than those of control group, ConA+ dexamethasone group and ConA+ GSK872 group (0.86±0.02 vs. 0.73±0.03, 0.68±0.02 and 0.72±0.03; 0.56±0.02 vs. 0.08±0.02, 0.11±0.01 and 0.08±0.01), however the proportion of CD45 + CD11b loF4/80 hi liver macrophages (Kupffer cells) was lower than those that of control group, ConA+ dexamethasone group and ConA+ GSK872 group (0.24±0.03 vs. 0.58±0.04, 0.52±0.07 and 0.56±0.07), and the differences were all statistically significant ( t=4.27, 5.90, 3.89, 18.70, 19.87, 20.52, 7.35, 3.82 and 3.87, all P<0.05). Conclusions:The number of macrophages incread in the livers of AIH patients. RIP3 signaling mediates the migration of monocytes/macrophages infiltration in immune hepatitis, which may be a potential therapeutic target for AIH.
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Objective:To observe and analyze the role of intestinal barrier in the pathognesis of autoimmune hepatitis (AIH), to explain the pathogenesis of AIH and to explore the intestinal based new treatment strategies.Methods:A total of 14 AIH patients from January to December 2017 at Tianjin Medical University General Hospital (six patients without liver cirrhosis, and eight patients with liver cirrhosis) and 10 healthy controls were enrolled. The serum levels of D-lactic acid (D-Lac) and diamine oxidase (DAO) were detected by enzyme-linked immunosorbent assay. Real time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of connexin (zonula occluden-1 (ZO-1), occludin), cytokines (interleukin(IL)-2, interferon(IFN)-γ, IL-4, IL-10) and Toll-like receptor 4 (TLR4) in terminal ileal tissues of each group. The relative expression of secretory immunoglobulin A (sIgA) in the terminal ileum was determined by Western blotting. Thirty BALB/c mice were selected and divided into blank control group, dextran sulfate sodium (DSS) group, concanavalin A (ConA) group, DSS+ ConA group, and DSS+ bacterium+ ConA group, with six mice in each group. The relative expression levels of ZO-1, occludin in mouse colonic tissues, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory activity degree of liver tissues (Knodell score) of each group were measured. T-test and one-way analysis of variance were performed for statistical analysis. Results:The serum D-Lac and DAO levels of AIH with liver cirrhosis group and AIH without liver cirrhosis group were both higher than those of healthy control group ((1 768.2±147.1) μg/L, (436.2±197.0) μg/L vs. (100.2±10.9) μg/L, and (11.5±2.5) U/L, (5.4±0.9) U/mL vs. (3.5±0.9) U/mL), and the levels of D-Lac and DAO of AIH with liver cirrhosis group were the highest; and the differences were statistically significant ( t=5.512, 36.010, 4.088 and 9.443, F=396.958 and 46.640, all P<0.01). The relative expression levels of ZO-1 and occludin in the terminal ileal mucosa of AIH with liver cirrhosis group were lower than those of healthy control group (0.20±0.14 vs. 1.67±0.51, 0.12±0.09 vs. 0.90±0.21), and the relative expression of ZO-1 in AIH without liver cirrhosis group was lower than that in healthy control group (0.99±0.37 vs. 1.67±0.51); and the differences were statistically significant ( t=8.641, 7.407 and 2.295, all P<0.05). The relative expression levels of IL-2 and IFN-γ in terminal ileal tissues of AIH with liver cirrhosis group were higher than those of healthy control group (1.11±0.43 vs. 0.24 ±0.16, and 3.50 ± 1.90 vs. 0.32±0.30), however the relative expression of sIgA in terminal ileal tissues was lower than that of healthy control group (0.506±0.024 vs. 1.081±0.102); and the differences were statistically significant ( t=4.679, 3.981 and 5.493, all P<0.05). While the relative expression levels of IL-10 in AIH with liver cirrhosis group and AIH without liver cirrhosis group were lower than that in healthy control group (0.30±0.20, 0.42±0.24 vs. 0.84± 0.23), and the relative expression levels of TLR4 in ileum mucosa of the both groups were higher than that of healthy control group (8.74 ±5.13, 6.74 ±3.65 vs. 0.89 ± 0.70); and the differences were statistically significant ( t=3.095, 4.816, 3.856 and 3.685, all P<0.05). The relative expression levels of ZO-1 and occludin of DSS+ ConA group were lower than those of ConA group (0.14±0.08 vs. 0.98±0.13, and 0.09±0.02 vs. 0.98±0.16), however serum ALT, AST levels and the Knodell score were all higher than those of ConA group ((5 496.67±618.83) U/L vs. (3 325.00±1 030.06) U/L, (8 825.00±1 165.35) U/L vs. (5 433.33±1 691.14) U/L, and 18.00±2.00 vs. 9.33±3.01); and the differences were statistically significant ( t=13.480, 13.520, 4.227, 4.045 and -2.892, all P<0.05). The relative expression levels of ZO-1 and occludin in DSS+ bacterium+ ConA group were higher than those in DSS+ ConA group (0.46±0.08 vs. 0.14±0.08, and 0.53±0.15 vs. 0.09±0.02), while serum ALT and AST levels were lower than those of DSS+ ConA group ((4 343.33±252.16) U/L vs. (5 496.67±618.83) U/L, and (6 123.33±1 086.60) U/L vs. (8 825.00±1 165.35) U/L); and the differences were statistically significant ( t=6.928, 7.122, 4.228 and 4.153, all P<0.01). Conclusions:AIH patients have increased intestinal permeability and impaired intestinal barrier which is more serious in patients with liver cirrhosis than in patients without cirrhosis. The intestinal barrier injury can aggravate ConA-induced immune-mediated liver injury. While the protection and repair of intestinal barrier can alleviate immune-mediated liver injury induced by ConA.
Résumé
Objective:To explore the clinical characteristics of liver function of patients with autoimmune liver disease (AILD) complicated with gallbladder stone (GS), so as to guide clinical practice.Methods:From November 2009 to October 2018, at General Hospital of Tianjin Medical University, the clinical data of 386 patients with AILD were retrospectively analyzed. According to the relevant diagnostic criteria, 208 cases of autoimmune hepatitis (AIH), 129 cases of primary biliary cholangitis (PBC) and 49 cases of PBC-AIH overlap syndrome were screened out. The incidence, clinical characteristics and the changes of laboratory indicators including albumin, alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) of AILD patients complicated with GS were analyzed. Chi-square test, t test and rank sum test were performed for statistical analysis. Results:There was no significant difference in the incidence between AILD, AIH, PBC and PBC-AIH overlap syndrome patients complicated with GS (32.9%, 127/386; 28.8%, 60/208; 36.4%, 47/129 and 40.8%, 20/49; respectively; P>0.05). Gallstones of AILD patients complicated with GS mostly were multiple and small stones with maximum diameter <1 cm (45.7%, 58/127 and 57.7%, 60/104, respectively). The age of initial diagnosis, the proportion of liver cirrhosis at inital diagnosis and the levels of ALP and GGT were higher in AILD patients complicated with GS than those of AILD patients without GS ((60.5±11.5) years vs. (57.6±11.5) years; 53.5%, 68/127 vs. 42.1%, 109/259; 154.00 U/L (89.00 U/L, 257.00 U/L) vs. 125.00 U/L (86.00 U/L, 212.00 U/L); 169.00 U/L (79.00 U/L, 343.00 U/L) vs. 128.60 U/L (48.00 U/L, 284.00 U/L); respectively); however the albumin level was lower than that of AILD patients without GS ((36.46±7.30) g/L vs. (38.34±7.58) g/L), and the differences were statistically significant ( t=-2.361, χ2=4.506, Z=-2.192, -2.443, t=2.322; all P<0.05). The incidence of GS in AILD patients≥60 years old was higher than that AILD patients<60 years old (37.6%, 73/194 vs. 28.1%, 54/192), and the difference was statistically significant ( χ2=3.948, P=0.047). The incidence of GS in AILD patients and AIH patients complicated with liver cirrhosis was higher than that in patients without liver cirrhosis (38.4%, 68/177 vs. 28.2%, 59/209; 35.7%, 35/98 vs. 22.7%, 25/110; respectively), and the differences were statistically significant ( χ2=4.506 and 4.259, P=0.034 and 0.039). Conclusions:AILD patients complicated with GS are common, most are multiple and small stones. When complicated with GS, the initial diagnosis may be delayed and the rate of liver cirrhosis at initial diagnosis may increase. The incidence of GS is high in AILD patients with older age and liver cirrhosis.
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In consideration of the current policies for scientific and technological achievement translation, the paper explored the model and strategy of such translation in medical institutions by analyzing typical cases of " orthopedic surgical robot" translation. Most common translation models in medical institutions are transfer or licensing. As hospitals lack the qualifications and conditions for product manufacturing and sales, " orthopedic surgical robot" was translated by means of a combined practice of both patent transfer and joint R&D with the enterprise under a strategic cooperation agreement. This practice not only manifested the contribution and interests of stakeholders in a rational way, but also guaranteed sustainable iterative R&D. Hospitals should launch cooperation with enterprises, universities or research organizations and form strategic alliances, and choose appropriate translation models based on their specifics, value and characteristics of the achievement flexibly.
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Objective@#To observe and analyze the role of intestinal barrier in the pathognesis of autoimmune hepatitis (AIH), to explain the pathogenesis of AIH and to explore the intestinal based new treatment strategies.@*Methods@#A total of 14 AIH patients from January to December 2017 at Tianjin Medical University General Hospital (six patients without liver cirrhosis, and eight patients with liver cirrhosis) and 10 healthy controls were enrolled. The serum levels of D-lactic acid (D-Lac) and diamine oxidase (DAO) were detected by enzyme-linked immunosorbent assay. Real time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of connexin (zonula occluden-1 (ZO-1), occludin), cytokines (interleukin(IL)-2, interferon(IFN)-γ, IL-4, IL-10) and Toll-like receptor 4 (TLR4) in terminal ileal tissues of each group. The relative expression of secretory immunoglobulin A (sIgA) in the terminal ileum was determined by Western blotting. Thirty BALB/c mice were selected and divided into blank control group, dextran sulfate sodium (DSS) group, concanavalin A (ConA) group, DSS+ ConA group, and DSS+ bacterium+ ConA group, with six mice in each group. The relative expression levels of ZO-1, occludin in mouse colonic tissues, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory activity degree of liver tissues (Knodell score) of each group were measured. T-test and one-way analysis of variance were performed for statistical analysis.@*Results@#The serum D-Lac and DAO levels of AIH with liver cirrhosis group and AIH without liver cirrhosis group were both higher than those of healthy control group ((1 768.2±147.1) μg/L, (436.2±197.0) μg/L vs. (100.2±10.9) μg/L, and (11.5±2.5) U/L, (5.4±0.9) U/mL vs. (3.5±0.9) U/mL), and the levels of D-Lac and DAO of AIH with liver cirrhosis group were the highest; and the differences were statistically significant (t=5.512, 36.010, 4.088 and 9.443, F=396.958 and 46.640, all P<0.01). The relative expression levels of ZO-1 and occludin in the terminal ileal mucosa of AIH with liver cirrhosis group were lower than those of healthy control group (0.20±0.14 vs. 1.67±0.51, 0.12±0.09 vs. 0.90±0.21), and the relative expression of ZO-1 in AIH without liver cirrhosis group was lower than that in healthy control group (0.99±0.37 vs. 1.67±0.51); and the differences were statistically significant (t=8.641, 7.407 and 2.295, all P<0.05). The relative expression levels of IL-2 and IFN-γ in terminal ileal tissues of AIH with liver cirrhosis group were higher than those of healthy control group (1.11±0.43 vs. 0.24 ±0.16, and 3.50 ± 1.90 vs. 0.32±0.30), however the relative expression of sIgA in terminal ileal tissues was lower than that of healthy control group (0.506±0.024 vs. 1.081±0.102); and the differences were statistically significant (t=4.679, 3.981 and 5.493, all P<0.05). While the relative expression levels of IL-10 in AIH with liver cirrhosis group and AIH without liver cirrhosis group were lower than that in healthy control group (0.30±0.20, 0.42±0.24 vs. 0.84± 0.23), and the relative expression levels of TLR4 in ileum mucosa of the both groups were higher than that of healthy control group (8.74 ±5.13, 6.74 ±3.65 vs. 0.89 ± 0.70); and the differences were statistically significant (t=3.095, 4.816, 3.856 and 3.685, all P<0.05). The relative expression levels of ZO-1 and occludin of DSS+ ConA group were lower than those of ConA group (0.14±0.08 vs. 0.98±0.13, and 0.09±0.02 vs. 0.98±0.16), however serum ALT, AST levels and the Knodell score were all higher than those of ConA group ((5 496.67±618.83) U/L vs. (3 325.00±1 030.06) U/L, (8 825.00±1 165.35) U/L vs. (5 433.33±1 691.14) U/L, and 18.00±2.00 vs. 9.33±3.01); and the differences were statistically significant (t=13.480, 13.520, 4.227, 4.045 and -2.892, all P<0.05). The relative expression levels of ZO-1 and occludin in DSS+ bacterium+ ConA group were higher than those in DSS+ ConA group (0.46±0.08 vs. 0.14±0.08, and 0.53±0.15 vs. 0.09±0.02), while serum ALT and AST levels were lower than those of DSS+ ConA group ((4 343.33±252.16) U/L vs. (5 496.67±618.83) U/L, and (6 123.33±1 086.60) U/L vs. (8 825.00±1 165.35) U/L); and the differences were statistically significant (t=6.928, 7.122, 4.228 and 4.153, all P<0.01).@*Conclusions@#AIH patients have increased intestinal permeability and impaired intestinal barrier which is more serious in patients with liver cirrhosis than in patients without cirrhosis. The intestinal barrier injury can aggravate ConA-induced immune-mediated liver injury. While the protection and repair of intestinal barrier can alleviate immune-mediated liver injury induced by ConA.
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Objective:To explore the application value of artificial intelligence-assisted diagnosis model based on convolutional neural network (CNN) in the differential diagnosis of benign and malignant breast masses.Methods:A total of 10 490 images of 2 098 patients with breast lumps (including 1 132 cases of benign tumor, 779 cases of malignant tumor, 32 cases of inflammation, 155 cases of adenosis) were collected from January 2016 to January 2018 in Beijing Tiantan Hospital Affiliated to the Capital University of Medical Sciences. They were divided into training set and test set and the auxiliary artificial intelligence diagnosis model was used for training and testing. Two sets of data training models were compared by two-dimensional imaging (2D) and two-dimensional and color Doppler flow imaging (2D-CDFI). The ROC curves of benign breast tumors, malignant tumors, inflammation and adenopathy were analyzed, and the area under the ROC curve (AUC) were calculated.Results:The accuracies of 2D-CDFI ultrasonic model for training group and testing group were significantly improved. ①For benign tumors, the result from training set with 2D image was: sensitivity 92%, specificity 95%, AUC 0.93; the result from training set with 2D-CDFI images was: sensitivity 93%, specificity 95%, AUC 0.93; the result for test set with 2D images was: sensitivity 91%, specificity 96%, AUC 0.94; the result for test set with 2D-CDFI images was: sensitivity 93%, specificity: 94%, AUC 0.94. ② For malignancies, the result for training set with 2D images was: sensitivity 93%, specificity 97%, AUC 0.94; the result for training set with 2D-CDFI images was: sensitivity 93%, specificity 96%, AUC 0.94; the result for test set with 2D images was: sensitivity 93%, specificity 96%, AUC 0.94; the result for test set with 2D-CDFI images was: sensitivity 93%, specificity 96%, AUC 0.94. ③For inflammation, the result for training set with 2D images was: sensitivity 81%, specificity 99%, AUC 0.91; the result for training set with 2D-CDFI images was: sensitivity 86%, specificity 99%, AUC 0.89; the result for test set with 2D images was: sensitivity 100%, specificity 98%, AUC 0.98; the result for test set with 2D-CDFI images was: sensitivity 100%, specificity 99%, AUC 0.96. ④For adenopathy, the result for training set with 2D images was: sensitivity 88%, specificity 97%, AUC 0.94; the result for training set with 2D-CDFI images was: sensitivity 93%, specificity 98%, AUC 0.94; the result for test set with 2D images was: sensitivity 94%, specificity 98%, AUC 0.93; the result for test set with 2D-CDFI images was: sensitivity 88%, specificity 99%, AUC 0.90. Its diastolic accuracy was not affected even if the maximum diameter of the tumor was less than 1 cm.Conclusions:Through the deep learning of artificial intelligence based on CNN for breast masses, it can be more finely classified and the diagnosis rate can be improved. It has potential guiding value for the treatment of breast cancer patients.