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Objective: To investigate the relationship between miR-199b and clinicopathologic features and prognosis of patients with colorectal cancer. Methods: Cancer tissues and adjacent normal tissues of 202 patients with colorectal cancer treated in Cancer Hospital of Chinese Academy of Medical Sciences from March to December 2011 were collected. Reverse transcription-quantitative real-time polymerase chain reaction was used to detect the expression level of miR-199b in colorectal cancer tissues and corresponding adjacent normal tissues. Kaplan-Meier method and Log rank test were used for survival analysis, and receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of miR-199b in colorectal cancer patients. Results: The relative expression level of miR-199b in colorectal cancer tissues (-7.88±0.11) was lower than that in adjacent normal tissues (-6.49±0.12, P<0.001). The expression level of miR-199b in colorectal cancer tissues with lymph node metastasis (-7.51±0.14) was higher than that in colorectal cancer tissues without lymph node metastasis (-8.23±0.17, P<0.001). The relative expression levels of miR-199b in stage Ⅰ/Ⅱ, Ⅲ and Ⅳ colorectal cancer tissues were gradually increased, which were -8.26±0.17, -7.70±0.16 and -6.57±0.27, respectively, and the difference was statistically significant (P<0.001). The 5-year survival rates of patients with high and low expressions of miR-199b were 75.6% and 84.6%(P=0.045) respectively. ROC curve showed that when miR-199b was -7.965, the area under the curve was 0.578 (95% CI: 0.468, 0.688). Conclusion: The high expression of miR-199b in colorectal cancer tissues is associated with late TNM stage, lymph node metastasis and poor prognosis in colorectal cancer patients, and miR-199b may be used as a potential marker for postoperative progress and prognosis in colorectal cancer patients.
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Humans , MicroRNAs/metabolism , Lymphatic Metastasis , Colorectal Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Prognosis , Gene Expression Regulation, Neoplastic , Kaplan-Meier EstimateABSTRACT
Objective:To explore the value of deep learning technology based on mammography in differentiating for breast imaging reporting and data system (BI-RADS) category 3 and 4 lesions.Methods:The clinical and imaging data of 305 patients with 314 lesions assessed as BI-RADS category 3 and 4 by mammography were analyzed retrospectively in Shenzhen People′s Hospital and Shenzhen Luohu People′s Hospital from January to December 2020. All 305 patients were female, aged 21 to 83 (47±12) years. Two general radiologists (general radiologist A and general radiologist B) with 5 and 6 years of work experience and two professional breast imaging diagnostic radiologists (professional radiologist A and professional radiologist B) with 21 years of work experience and specialized breast imaging training were randomly assigned to read the imaging independently at a 1∶1 ratio, and then to read the imaging again in combination with the deep learning system. Finally, breast lesions were reclassified into BI-RADS category 3 or 4. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the diagnostic performance, and the differences of AUCs were compared by DeLong method.Results:The AUC of general radiologist A combined with deep learning system to reclassify BI-RADS category 3 and 4 breast lesions was significantly higher than that of general radiologist A alone (AUC=0.79, 0.63, Z=2.82, P=0.005, respectively). The AUC of general radiologist B combined with deep learning system to reclassify BI-RADS category 3 and 4 breast lesions was significantly higher than that of general radiologist B (AUC=0.83, 0.64, Z=3.32, P=0.001, respectively). There was no significant difference in the AUCs between professional radiologist A combined with deep learning system and professional radiologist A, and professional radiologist B combined with deep learning system and professional radiologist B in reclassifying BI-RADS category 3 and 4 breast lesions ( P>0.05). Conclusion:The deep learning system based on mammography is more effective in assisting general radiologists to differentiate between BI-RADS category 3 and 4 lesions.
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Sarcopenia is an age-related syndrome with progressive, generalized loss of muscle mass, strength, and physiological function. Low muscle mass is an important diagnostic criterion for sarcopenia. Ultrasound is safe, convenient and cost-effective, with extensive availability. It's a promising diagnostic tool for muscle mass assessment and sarcopenia screening in the elderly population. This review focuses on the specific methods and latest research progress on ultrasound assessment of sarcopenia.
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Two new ursane triterpenoids along with twelve known compounds were isolated from 80% ethanol extract of Agastache rugosa (Fisch. et. Mey.) O. Kuntze by using silica gel column, MCI column, ODS column and HPLC. The structures of the new compounds were identified as 2α,3α-dihydroxy-24-nor-urs-4(23),12(13)-dien-28-oic acid (1) and 2α,3α-dihydroxy-24-nor-urs-4(23),12(13),20(30) -trien-28-oic acid (2) by HR-ESI-MS, NMR and ECD spectral data, named agasursacid A and agasursacid B. In addition, compounds 3, 4, 6, 8 showed anti-coxsackievirus B3 (CVB3) activities with a IC50 as 4.77, 1.59, 11.11 and 25.87 μmol·L-1, resepectively.
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ObjectiveTo investigate the effect and mechanism of Scutellaria Baicalensis polysaccharides on intestinal immunity in mice with ulcerative colitis （UC）. MethodsC57BL/6 mice were randomly assigned to blank group， model group， mesalazine group and Scutellaria Baicalensis polysaccharides low-dose， medium-dose and high-dose groups （n=10 mice/group）. The daily status of mice was observed and the disease activity index （DAI） score was recorded. The expression of cytokines including IL-6， IL-17 and IL-23 in serum was detected by ELISA. After the mice were sacrificed， HE was used to observe the intestinal mucosal damage in mice， and the colonic tissue damage index （TDI） score was recorded. Western blot and immunohistochemistry were used to detect the expression levels of Janus kinase 2 （JAK2）， signal transducer and activator of transcription （STAT3）， p-JAK2 and p-STAT3 proteins. ResultsCompared with the blank group， the DAI score of the model group was significantly increased， the contents of IL-6， IL-17 and IL-23 in serum were significantly increased， the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in colon tissue was significantly increased， and the expression levels of p-JAK2 and p-STAT3 were significantly increased. Compared with the model group， the DAI score of mice in each administration group was significantly decreased. The contents of IL-6， IL-17 and IL-23 in serum were decreased， the TDI score was decreased， the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in colon tissue was decreased， and the expression of p-JAK2 and p-STAT3 was decreased. ConclusionScutellaria Baicalensis polysaccharides may improve the inflammatory effect of UC mice through JAK2/STAT3 pathway and IL-23/IL-17 inflammatory axis.
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Objective:To construct a sensitive index system of nursing quality for patients with acute ischemic stroke patients undergoing interventional thrombectomy, so as to provide a scientific basis for interventional thrombectomy care for acute ischemic stroke.Methods:Taking the "structure-process-result" three-dimensional quality model as the theoretical framework, through evidence-based literature search, the item pool was drawn up, and finally the indicators and their weights at each level were determined by two rounds of Delphi method in December 2021 and January 2022 and analytic hierarchy process.Results:The positive coefficients of the two rounds of inquiries to experts were 0.92 and 1.00, respectively, the authority coefficients were 0.913 and 0.917, and the Kendall coefficients were 0.141 and 0.202, respectively. The final index system consisted of 3 primary indicators, 9 secondary indicators and 50 three-level indicators.Conclusions:The nursing sensitive quality index system for patients with acute stroke patients undergoing interventional thrombectomy constructed in this study has high reliability and scientificity, which can provide target incentives for clinical nurses and provide reference for the development of specialized nursing sensitive quality indicators.
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Peripheral retinal degeneration is a typical lesion in ophthalmic clinical practice. Each type of degeneration affects distinct retinal layers and may lead to sight-threatening complications. Due to its specific location, where current ophthalmic imaging technologies have difficulties observing, the pathogenesis remains unclear despite previous works. This review outlines the characteristics of peripheral retinal degeneration by different wide-field imaging technologies, including ultra-wide field fundus imaging, wide field spectral domain optical coherence tomography, optical coherence tomography angiography and fundus fluorescein angiography, as well as new perspectives on their pathogenesis or pathological characteristics so as to provide new ideas for clinical diagnosis and management. Due to the small size of sample and the lack of prospective and long-term observation of multimodal imaging, it is still impossible to comprehensively evaluate the progression and risk of different types of degeneration. Therefore, it is expected that wide-field multimodal imaging technology will be more widely applied to study the mechanism of peripheral retinal degeneration and guide the clinical practice options.
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AIM: To investigate the effects of modified Zhujing Pill on the mitochondrion structure and dynamin-related protein of retinal pigment epithelial cells(RPEs)in mice with form deprivation myopia.METHODS: 3-week-old C57BL/6J mice were randomly divided into control group, model group and Chinese medicine group, with 10 mice in each group. Myopia model of the right eye of mice was established by means of form deprivation in model and Chinese medicine groups. After 4wk, the Chinese medicine group were given intragastric administration of modified Zhujing Pill suspension 0.546g/(kg·d)(0.2mL/d)for 4wk, and same amount of saline was given to mice in other groups at the same time of modeling. The axial length and diopter of the right eye of the mouse were measured before and after the experiment by A-ultrasound and a strip retinoscope respectively. At the end of the experiment, the mitochondrial ultrastructure of RPEs was observed by transmission electron microscope. Western blot, and real-time fluorescent quantitative PCR(q-PCR)were used to detect quantitative and gene expression of mitofusin 1(MFN1), optic atrophy 1(OPA1), and dynamin-related protein 1(DRP1)in retinal tissues respectively.RESULTS: At the beginning of the experiment, there was no statistically significant difference in axial length and diopter of the right eye of the mouse in control, model and Chinese medicine groups(P>0.05). At the end of the experiment, compared with the control group, the mice in the model group and the Chinese medicine group had lower diopter and continuously prolonged axial length(all P<0.05), while the mice in the Chinese medicine group had significantly shorter axial length and higher diopter than the model group(all P<0.05). Western blot and q-PCR results showed that the relative expression of MFN1 and OPA1 decreased and DRP1 increased in both the model group and the Chinese medicine group compared with the control group(all P<0.05), and the relative expression of MFN1 and OPA1 increased in the Chinese medicine group compared with the model group(all P<0.05). The electron microscopic results showed that the mitochondria in the right retina of the mice were only mildly swollen in the Chinese medicine group, while the mitochondria in the model group were obviously swollen and disordered and empty.CONCLUSION: Modified Zhujing Pill could protect the retinal mitochondria by regulating the key proteins of mitochondrial dynamics(MFN1, OPA1, and DRP1), and it has a protective effect on the retina of axial myopic mice.
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【Objective】 To investigate the trend of neutralizing antibody level in plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine. 【Methods】 Three commercial ELISA kits for novel coronavirus neutralization antibody detection, manufactured by Company A, B and C, were chosen and screened by Pseudotype Neutralization Test from December 2021 to June 2022. A total of 410 plasma samples from 64 plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine and there after donated plasma within six months were detected by the selected ELISA kit from July to October, 2022. The data were analyzed by Excel 2013 and SPSS 26 software. 【Results】 The high-throughput ELISA kit for SARS-CoV-2 neutralizing antibody detection, manufactured by Company A, was selected for further antibody titer detection. The mixed plasma titers were 1 337.34, 1 148.89, 852.19, 681.38, 556.44 and 457.19 U/mL from 1 to 6 months, respectively, after the 3rd shot of vaccine. The neutralizing antibody titer level began to increase around 7 days after the 3rd shot of vaccine injection and peaked (peak range: 264.07-2 208.39 U/mL, median: 569.34 U/mL) at 1 month (range: 9-43 days, median: 22 days), and then gradually decreased (P<0.05). 【Conclusion】 The neutralizing antibody titer of plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine began to rise around 7 days after vaccination, which reached the peak value at around 1 month and then gradually decreased.
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Pachychoroid spectrum diseases(PSD)have been defined as a group of diseases with similar choroidal features and pathological processes, such as central serous chorioretinopathy(CSC), polypoidal choroidal vasculopathy(PCV), etc. The main features are the changes in the thickness of vascular layers of the choroid and increasing vascular permeability. The development of modern ophthalmic imaging devices represented by optical coherence tomography angiography(OCTA)allowed intuitive investigation of the changes in the choroidal vascular layers, which gives a new insight into the pathogenesis of this spectrum diseases. This article summarizes the common clinical characteristics of healthy individuals and PSD and reviews the latest imaging findings. Whether each type of PSD is a phenotype of the same disease at different stages or other with similar characteristics was discussed from different perspectives, such as genetic background and anatomical structure, providing a reference for the study of pathogenesis, early clinical diagnosis, and prevention and treatment of this disease.
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Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.
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Objective:To determine the epidemiology of hyperkalemia and influencing factors in a general population in Pinggu district of Beijing city.Methods:This study was a cross-sectional survey. The subjects were from the epidemiological survey population of chronic diseases in Pinggu district of Beijing city from March to May 2014. All participants completed a questionnaire, anthropological measurement, and venous blood samples collection to detect serum creatinine and potassium and so on. First void morning urine was collected to detect the albumin-creatinine ratio. Hyperkalemia and hypokalemia were defined as serum potassium level>5.0 mmol/L and≤3.5 mmol/L, respectively. Logistic regression analysis method was used to analyze the influencing factors of hyperkalemia.Results:Of the 10 252 people in this study, the prevalence of hyperkalemia was 6.17%(95% CI 5.70%-6.67%), the prevalence of hypokalemia was 0.61%(95% CI 0.47%-0.79%), and the prevalence of participants with serum potassium>5.5 mmol/L was 0.53%(95% CI 0.40%-0.69%). Multivariate logistic regression analysis results showed that males ( OR=1.269, 95% CI 1.074-1.498, P=0.005), diabetes ( OR=1.226, 95% CI 1.008-1.490, P=0.041), increased total cholesterol ( OR=1.219, 95% CI 1.119-1.329, P<0.001), and decreased estimated glomerular filtration rate ( OR=0.971, 95% CI 0.965-0.977, P<0.001) were significantly correlated with the increased risk of hyperkalemia. Usage of renin-angiotensin-aldosterone system inhibitors and diuretics were not found to be significantly associated with the risk of hyperkalemia ( OR=1.018, 95% CI 0.751-1.380, P=0.908; OR=0.638, 95% CI 0.229-1.781, P=0.391). Conclusions:The prevalence of HK in the general population is 6.17%. The male, decreased estimated glomerular filtration rate, diabetes, and increased total cholesterol are influencing factors of hyperkalemia.
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Objective:To analyze the clinical and pathological characteristics, treatment and prognosis of renal changes in patients with Kimura disease and improve the clinicians′ understanding on renal manifestations of Kimura disease.Methods:The clinical data of Kimura disease patients with definite diagnosis and detailed data in Peking Union Medical College Hospital from January 1980 to August 2020 were retrospectively analyzed. The patients were divided into renal impairment group and non-renal impairment group according to whether the kidney was involved or not and the related clinical data between the two groups were compared. The patients presenting with nephrotic syndrome were followed up.Results:There were 60 patients with Kimura disease confirmed by pathological diagnosis with 48 males. The median age was 33(3, 62) years old, and the median duration was 36(12, 111) months. There were 18 cases complicated with renal injury in 49 patients with complete routine urine and renal function examination and the main manifestations of renal injury were proteinuria and/or microscopic hematuria. There was no significant difference at age, sex and absolute value of eosinophils between the two groups (all P>0.05). Compared with the renal inpairment group, patients in non-renal inpairment group had longer course of disease, higher levels of hypersensitive C-reactive protein and erythrocyte sedimentation rate, and lower median values of total eosinophils and total IgE, but there was no statistically significant difference (all P>0.05). Among the patients with renal involvement, 6 patients met the diagnostic criteria for nephrotic syndrome, and 5 of them completed renal biopsies. The renal pathological diagnosis was membranous nephropathy in 2 cases and minimal change disease in 3 cases, and no interstitial eosinophil infiltration was found in renal biopsy tissues. These patients had a good response to glucocorticoids and/or immunosuppressive therapy, and achieved complete remission of nephrotic syndrome; at the same time, lymphadenopathy caused by Kimura disease could be well controlled. Conclusions:Kimura disease can combine with various renal lesions, and the pathology of nephrotic syndrome can be membranous nephropathy or minimal change nephropathy. After energetic treatment of glucocorticoids and/or immunosuppressive therapy, nephrotic syndrome can be completely relieved, and lymphadenopathy can be well controlled. The relationship between Kimura disease and renal disease needs further study.
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Objective:To investigate the value of 18F-FDG PET/CT metabolic parameters in predicting perineural invasion (PNI) in patients with non-metastatic rectal cancer. Methods:From August 2012 to April 2020, 81 patients (51 males, 30 females, median age: 63 years) who received PET/CT examination and pathologically confirmed as rectal cancer in the Affiliated Hospital of Qingdao University were retrospectively analyzed. The 18F-FDG PET/CT metabolic parameters including SUV max, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and clinicopathological factors including gender, age, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, maximum tumor diameter, degree of differentiation, T stage, lymph node metastasis, and TNM stage were recorded. Mann-Whitney U test and χ2 test were used to compare the differences of each parameter between PNI positive group and PNI negative group. Multivariate logistic regression was used to analyze the independent predictor of positive PNI. ROC curve was used to analyze its predictive efficacy. Results:Of 81 patients, 32(39.51%) were PNI positive and 49(60.49%) were PNI negative. There were significant differences of T stage ( χ2=10.73, P=0.010), lymph node metastasis ( χ2=6.21, P=0.013), TNM stage ( χ2=7.61, P=0.022), MTV (14.6(10.4, 24.7)and 9.0(5.4, 14.5) cm 3; U=-3.48, P=0.001) and TLG (108.588(72.749, 182.707) and 65.365(35.593, 117.682) g; U=-2.79, P=0.005) between PNI positive group and PNI negative group. Multivariate logistic regression analysis showed that MTV was the independent predictor of positive PNI in non-metastatic rectal cancer patients (odds ratio ( OR)=1.130, 95% CI: 1.025-1.245, P=0.014). The optimal threshold of MTV was 9.53 cm 3 and AUC was 0.73 with the sensitivity of 81.82%(27/33) and the specificity of 59.18%(29/49). Conclusion:18F-FDG PET/CT metabolic parameter MTV can predict PNI in non-metastatic rectal cancer with high sensitivity.
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Objective:To explore the clinical features and risk factors of systemic lupus erythematosus(SLE) concomitant with interstitial lung disease(ILD) in children.Methods:A retrospective analysis was performed.A total of 111 hospitalized children diagnosed with SLE in the Department of Rheumatology and Immunology, Children′s Hospital of Soochow University from February 2016 to November 2018 were selected as the research subjects and divided into the SLE-ILD group(18 cases) and the SLE-non-ILD group(93 cases)according to the lung high-resolution CT manifestations. T-test and Wilcoxon rank sum test were used to compare and analyze the general situation, clinical manifestations and laboratory results.Multivariate Logistic regression was used to analyze the risk factors of SLE-ILD. Results:The prevalence of SLE-ILD was 16.2%(18/111 cases). There were significant differences between the SLE-ILD group and the SLE-non-ILD group in the course of disease [14.00 (12.00-24.25) months vs.1.00(1.00-2.00) months], the incidence of serositis [55.6%(10/18 cases) vs.8.6%(8/93 cases)], post-activity shortness of breath [83.3%(15/18 cases) vs.25.8%(24/93 cases)], nervous system damage [27.8%(5/18 cases) vs.6.5%(6/93 cases)], cardiovascular system damage [38.9%(7/18 cases) vs.9.7%(9/93 cases)], the occu-rrence of increased erythrocyte sedimentation rate [66.7%(12/18 cases) vs.31.2%(29/93 cases)], the decreased C 3[88.9%(16/18 cases) vs.62.4%(58/93 cases)], positive anti neutrophil cytoplasmic antibody (ANCA) [88.9%(16/18 cases) vs.18.3%(17/93 cases)], positive anti-Sm antibody [61.1%(11/18 cases) vs.15.1%(14/93 cases)] and anti ribonucleoprotein antibody (anti RNP antibody)[66.7%(12/18 cases) vs.16.1%(15/93 cases)](all P<0.05). Logistic regression analysis demonstrated that serositis( OR=30.535, 95% CI: 2.167-430.336, P=0.011), shortness of breath after exercise( OR=55.115, 95% CI: 1.117-2 579.852, P=0.041), positive ANCA( OR=65.090, 95% CI: 4.488-944.071, P=0.002) and positive anti-RNP antibody( OR=10.007, 95% CI: 1.362-73.500, P=0.024) were risk factors for SLE-ILD. Conclusions:The longer the course of SLE, the higher the incidence of ILD; serositis, shortness of breath after exercise, positive ANCA and positive anti RNP antibody may be risk factors for SLE-ILD.
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Objective:To investigate the potential risk factors for cryptogenic stroke (CS) in patients with patent foramen ovale (PFO).Methods:Patients underwent PFO closure in the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from June 2018 to December 2021 were enrolled retrospectively. Transesophageal echocardiography was used to evaluate the morphological characteristics of foramen ovale and right-to-left shunt (RLS). Multivariate logistic regression analysis was used to determine the independent risk factors for CS in patients with PFO. Results:A total of 203 patients with PFO were enrolled. Their age was 41.9±14.3, and 116 patients (57.1%) were male. There were 102 patients in CS group and 101 patients in non-stroke group. The age, body mass index, systolic blood pressure and diastolic blood pressure, and the constituent ratios of male, hypertension, diabetes, hyperlipidemia and smoking of the CS group were significant higher than those of the non-stroke group (all P<0.05). The PFO channel of the CS group was longer, wider and more combined with resting RLS (all P<0.05). Multivariate logistic regression analysis showed that systolic blood pressure (odds ratio [ OR] 1.065, 95% confidence interval [ CI] 1.022-1.111; P=0.003), PFO length ( OR 1.124, 95% CI 1.004-1.258; P=0.043) and resting RLS ( OR 5.449, 95% CI 2.283-13.004; P<0.001) were the independent risk factors for CS in patients with PFO. Conclusion:Systolic blood pressure, PFO length and the presence of resting RLS are the independent risk factors for CS in patients with PFO.
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AIM: To investigate the effect of modified Zhujing pill on retinal autophagy in mice with form deprivation myopia.METHODS: Thirty C57BL/6 mice were randomly divided into a negative control group, a myopia model group and a traditional Chinese medicine intervention group, with 10 mice in each group. Except for the negative control group, all mice in the myopia model group and the traditional Chinese medicine intervention group used translucent EP tubes to cover their right eyes to make a form deprivation myopia(FDM)model; The traditional Chinese medicine intervention group gavage Zhujing pill modified suspension 0.546g/(kg·d)(0.15mL/d), the negative control group and the myopia model group were given an equal amount of normal saline(0.15mL/d)for 4wk. At the beginning and the end of the experiment respectively, the right eye diopter of the mouse was measured with a strip retinoscope, measurement of the axial length of the right eye of mouse by A-ultrasound. At the end of the experiment, the right eyes of all mice were taken for detection, and immunofluorescence method was used to locate and detect the activity and migration of the retinal microglia marker(Iba1); Transmission electron microscope observation of autophagosome formation in retinal pigment epithelial cells; Western Blot, real-time fluorescent quantitative PCR(q-PCR)to detect the autophagy marker LC3Ⅱ and p62 protein quantitative and gene expression in retinal tissues.RESULTS: At the end of the experiment, the refractive power of the right eyes of mice showed that the myopia model group and the traditional Chinese medicine intervention group formed relative myopia, the myopia model group and the traditional Chinese medicine intervention group were significantly lower than those of the negative control group(all P<0.01). At the end of the experiment, the axial length of the myopia model group and the Chinese medicine intervention group were significantly increased compared with the negative control group(P<0.01). Immunofluorescence method for locating and detecting Iba1 showed that the average optical density of Iba1 in the retina of the myopia model group increased the most obviously, followed by the increase in the negative control group, and the decrease in the traditional Chinese medicine intervention group. Compared with the negative control group, the myopia model group increased significantly(P<0.05), and the traditional Chinese medicine intervention group was significantly lower than the myopia model group(P<0.05). It was found that Iba1 migrated to the ganglion cell layer in the myopia model group and the traditional Chinese medicine intervention group. Transmission electron microscopy showed that autophagosomes were observed in the retinal pigment epithelial cells of the myopia model group and the Chinese medicine intervention group. The results of Western Blot and q-PCR showed that the expression of LC3Ⅱ and p62 increased most obviously in the traditional Chinese medicine intervention group, followed by the myopia model group, and the negative control group was the lowest.CONCLUSION: The results of the study show that modified Zhujing pill may enhance retinal autophagy in mice with FDM by inhibiting the activation of microglia.
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The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.
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Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.
Subject(s)
Animals , Mice , AMP-Activated Protein Kinases/metabolism , Insulin/metabolism , Lipolysis/physiology , Liver/metabolism , Tandem Mass SpectrometryABSTRACT
Objective:To establish the predictive models for the prognosis of ductal carcinoma in situ (DCIS) at different pathological stages, and to evaluate the predictive performance of the models.Methods:Complete data of 273 patients with confirmed DCIS at different pathological stages who underwent mammography examination in Shenzhen People′s Hospital, Peking University Shenzhen Hospital and Shenzhen Luohu People′s Hospital from November 2014 to December 2020 were retrospectively collected, including 110 cases in the DCIS+ductal carcinoma in situ with microinvasion (DCIS-MI) group and 163 cases in the invasive ductal carcinoma (IDC)-DCIS group. The clinical, imaging and pathological features were analyzed. Mammary Mammo AI fusion model and deep learning-based natural language processing (NLP) structured diagnostic report model were used for image feature extraction. Patients in each group were randomly divided into training set and validation set with a ratio of 6∶4, and the predictors were screened by univariate and multivariate logistic regression analysis. The lowest Akaike information criterion value of each group was selected to construct the final predictive model. The receiver operating characteristic (ROC) curve was drawn to evaluate the performance of each model.Results:Taking estrogen receptor (-) or human epidermal growth factor receptor 2 (3+) as the poor prognostic reference, there were 62 cases considered with poor prognosis and 48 cases with good prognosis in DCIS+DCIS-MI group; while in the IDC-DCIS group, taking the Nottingham prognostic index as the reference, 33 cases were considered with poor prognosis, 73 cases with moderate prognosis, and 57 cases with good prognosis. Four predictive factors were screened to construct the DCIS+DCIS-MI-group predictive model, including DCIS nuclear grade, calcification with suspicious morphology in mammography, DCIS pathologic subtype and DCIS with microinvasion. Five predictive factors were screened to construct the IDC-DCIS-group predictive model, including neural or vascular invasion, Ki67 level, DCIS subtype, DCIS component proportion and associated features in mammography. The area under curve (AUC) for predicting poor prognosis of DCIS+DCIS-MI was 0.92 (95%CI 0.84-1.00) in the training set and 0.90 (95%CI 0.82-0.99) in the validation set; while the AUC for predicting poor prognosis of IDC-DCIS was 0.84 (95%CI 0.76-0.93) in the training set and 0.78 (95%CI 0.64-0.91) in the validation set.Conclusion:The developed models based on deep learning combined with NLP can effectively predict the prognosis of DCIS at different pathological stages, which are beneficial to the risk stratification of patients with DCIS, providing a reference for clinical decision.