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Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.
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AIM To explore the effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure(CRF)and its mechanism.METHODS Wistar rats were randomly divided into the blank group for normal feeding and the model group for the establishment of CRF rat models by 5/6 nephrectomy.Subsequently,the successfully established rat models were randomly divided into the model group,the Heidihuang Pills group(10.43 g/kg),and the Heidihuang Pills+IGF-1R blocker(JB1)group for a regimen of 7-day subcutaneous injection of 18 μg/kg JB1 followed by gavage of 10.43 g/kg Heidihuang Pills.Eight weeks after the administration,the rats had their serum levels of Scr and BUN detected;their pathological changes of renal tissue observed by HE and Masson staining;their renal protein expressions of TGF-β,HIF-1α and α-SMA detected by immunohistochemistry;their renal protein expressions of IGF-1R and TGF-β detected by Western blot;and their renal mRNA expressions of IGF-1R and TGF-β detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed increased serum levels of Scr and BUN(P<0.05);increased,degree of renal fibrosis,and renal fibrosis area(P<0.05);increased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P<0.05);and decreased expressions of IGF-1R mRNA and protein(P<0.05).Compared with the model group,the Heidihuang Pills group displayed decreased serum Scr and BUN levels(P<0.05);decreased inflammatory cells in renal interstitium and the fibrosis degree(P<0.05);decreased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P<0.05);and increased expressions of IGF-1R mRNA and protein(P<0.05).However,the administration of JB1 could weaken the improvement effect of Heidihuang Pills on renal fibrosis in CRF rats(P<0.05).CONCLUSION Heidihuang Pills can inhibit the renal fibrosis in CRF rats,and the inhibition process is related to up-regulated IGF-1 expression and promoted combination of IGF-1 and IGF-1R.
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AIM: To explore the feasibility of swept source optical coherence tomography angiography(SS-OCTA)in evaluating early retinal and choroidal microcirculation changes in patients with hypertension.METHODS:Prospective clinical study. A total of 27 patients with grade 2 or 3 essential hypertension(hypertension group)diagnosed in the Department of Cardiology of Xi'an First Hospital from July to November 2022 were included in the study. There were 14 males and 13 females. The mean age was(57.11±3.36)years. During the same period, 27 age- and sex-matched normal people without a history of hypertension were selected as the control group, including 12 males and 15 females. The average age was(55.74±2.95)years old. All patients underwent BCVA(LogMAR), intraocular pressure, axial length, slit lamp examination, fundus color photography and SS-OCTA examination. SS-OCTA was used to scan the macular area of the right eye in the range of 6×6 mm. The retina and choroid were divided into three concentric circles with diameters of 0-1 mm, 1-3 mm and 3-6 mm around the fovea according to ETDRS. Macular vessel density(VD), perfusion area(PA), retinal thickness(CMT), choroidal thickness(CT), choroidal vessel volume(CVV)and choroidal vasculr index(CVI)of the superficial capillary plexus(SCP)and the deep capillary plexus(DCP)in the macular area of 0-1 mm, 1-3 mm and 3-6 mm were analyzed and recorded. The changes in VD, PA, CMT, CT, CVV and CVI were compared between the two groups. Independent sample t-test was used to compare VD, PA, CMT and CVI between the two groups; CT, CVV and LogMAR visual acuity were analyzed by Wilcoxon signed rank test of independent samples.RESULTS:Compared with the control group, the hypertensive group had significantly lower VD in the macular area 0-3 mm(0-1 mm, t=-3.144; 1-3 mm, t=-3.611, P<0.05). VD in the area of 3-6 mm showed a tendency to increase compared with the control group(t=1.715, P>0.05). The CMT in the 0-1mm area of the macular area in the hypertension group was lower than that in the control group(t=-2.624, P<0.05). There was no significant difference in CT, CVV and CVI between the two groups(P>0.05).CONCLUSION:The VD of DCP in the 0-3 mm area and the CMT in the 0-1 mm area are decreased in hypertensive patients. There were no significant differences in CT, CVV and CVI between the two groups. VD and CMT in macular DCP may be used as indicators to evaluate the early changes of retinal and choroidal microcirculation in hypertensive patients.
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Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.
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Idoso , Masculino , Humanos , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/patologia , Estudos Retrospectivos , Volume Sistólico , Estudos de Casos e Controles , Ácidos Nucleicos , 8-Hidroxi-2'-Desoxiguanosina , Miócitos Cardíacos/patologia , RNA , Estresse Oxidativo , Guanina , Função Ventricular EsquerdaRESUMO
Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.
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Idoso , Masculino , Humanos , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/patologia , Estudos Retrospectivos , Volume Sistólico , Estudos de Casos e Controles , Ácidos Nucleicos , 8-Hidroxi-2'-Desoxiguanosina , Miócitos Cardíacos/patologia , RNA , Estresse Oxidativo , Guanina , Função Ventricular EsquerdaRESUMO
Objective To study the correlation between regional cerebral glucose metabolism and behavioral scores in middle cerebral artery occlusion(MCAO)model rats before and after the intervention of constraint induced movement therapy(CIMT),and the correlation between the natural recovery processand motor function recovery in MCAO model rats and the brain activation after CIMT intervention,and to further explore the mechanism of CIMT. Methods Twenty-two adult male Sprague-Dawley(SD)rats were randomly divided into an ischemic group treated with CIMT (CIMT,n=6),an ischemic group (Control,n=6),a sham-operated group(Sham,n=6),and a blank control group(Normal,n=4). The MCAO models of rats in the CIMT group and Control group were established by thread embolism method. The middle cerebral artery was not blocked during the operation for the Sham group,and the Normal group was not given any special treatment. After operation,rats in the CIMT group and Sham group were treated with CIMT. On the 7th day(d7)and the 22nd day(d22)after surgery,foot-fault test(FFT)and the beam balance and walking (BBW) test were used to evaluate the forelimb motor;micro positron emission tomography-computed tomography (micro PET/CT) imaging with fluorodeoxyglucose (18F-FDG) was used to scan the glucose metabolism in different brain regions of rats;Pearson correlation analysis was used to analyze the correlation between behavioral scores and glucose metabolism level in the CIMT group and Control group. Results On d7,the BBW score in the CIMT group and Control group was negatively correlated with glucose metabolism in the left insular cortex and the auditory cortex,and positively correlated with glucose metabolism in the right posterior hippocampus,superior colliculus,and inferior colliculus,with statistically significant differences;the FFT score was negatively correlated with glucose metabolism in the left somatosensory cortex, insular cortex and orbitofrontal cortex, and positively correlated with glucose metabolism in the right midbrain,with statistically significant differences. On d22, the BBW score in the CIMT group and Control group was positively correlated with glucose metabolism in the amygdala,caudate putamen,insular cortex and entorhinal cortex,and negatively correlated with glucose metabolism in the nucleus accumbens (Acb) core shell and caudate putamen in the right brain region,with statistically significant differences;the FFT score was negatively correlated with the entorhinal cortex in the right hemisphere and the difference was statistically significant. Conclusion The recovery of motor function promoted by CIMT was associated with the activation of both cerebral hemispheres in rats. The improvement of balance function promoted by CIMT in rats with cerebral ischemia was mainly related to the activation of Acb core shell in the right hemisphere. The recovery of fine grasping function promoted by CIMT may be related to the activation of the right entorhinal cortex.
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Objective: To summarize the clinical characteristics of heart failure patients with recovered ejection fraction (HFrecEF) and identify variables capable of predicting left ventricular ejection fraction (LVEF) recovery. Methods: This case control study included patients with heart failure, who admitted to Department of Cardiology of Beijing Hospital from January 1, 2009 to December 31, 2017. The patients were divided into 3 groups based on the baseline LVEF and changes of LVEF: heart failure with reduced ejection fraction (HFrEF, baseline LVEF≤40%, follow-up LVEF≤40% or follow-up LVEF>40% but LVEF increase<10% from baseline), HFrecEF(baseline LVEF≤40%, follow-up LVEF>40% and increase≥10% from baseline), and heart failure with preserved ejection fraction (HFpEF, baseline LVEF>40%). Clinical data were collected and endpoint events (all-cause death, cardiovascular death and sudden death) were recorded. The Log-rank test was used to evaluate the differences of terminal events in different groups, and Kaplan-Meier survival analysis was performed. Logistic regression equation was used to identify prognostic factors of HFrecEF. Results: A total of 310 patients with heart failure were included. There were 91(29.4%) HFrEF patients, 38(12.3%) HFrecEF patients and 181(58.4%) HFpEF patients. Compared with HFrEF patients and HFpEF patients, HFrecEF patients were featured by younger age, more likely to be female, higher systolic blood pressure, diastolic blood pressure and resting heart rate (all P<0.05). Dilated cardiomyopathies were more common, while old myocardial infarctions were less common in HFrecEF (both P<0.05). During a median follow-up of 36.7(18.0, 63.9) months, Kaplan-Meier survival analysis found that HFrecEF patients had the lowest all-cause mortality (Log-rank P=0.047, HFrecEF vs. HFpEF P=0.017, HFrecEF vs. HFrEF P=0.016, and HFpEF vs. HFrEF P=0.782).The cardiovascular mortality ranged from low to high was in HFrecEF patients, HFpEF patients, and HFrEF patients (Log-rank P<0.001, HFrecEF vs. HFpEF P=0.029, HFrecEF vs. HFrEF P<0.001, HFrEF vs. HFpEF P=0.005). Sudden death rate was similar among the three groups (Log-rank P=0.520). Logistic regression analysis showed that left ventricular end-diastolic diameter (LVEDD)≤55 mm (OR=5.922, 95%CI 1.685-20.812, P=0.006), higher diastolic blood pressure (OR=1.058, 95%CI 1.017-1.100, P=0.005), faster resting heart rate (OR=1.042, 95%CI 1.006-1.080, P=0.024), absence of old myocardial infarction (OR=5.343, 95%CI 1.731-16.488, P=0.004) were independent prognostic factors of LVEF recovery after clinical treatment. Conclusions: Patients with HFrecEF are associated with a better prognosis as compared to patients with HFrEF and HFpEF. LVEDD≤55 mm, higher diastolic blood pressure, faster heart rate,and absence of old myocardial infarction are independent prognostic factors of LVEF recovery after clinical treatment.
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Feminino , Humanos , Masculino , Estudos de Casos e Controles , Insuficiência Cardíaca , Prognóstico , Volume Sistólico , Disfunção Ventricular Esquerda , Função Ventricular EsquerdaRESUMO
The terpenoids in Pogostemon cablin have complex structures and abundant pharmacological effects. Patchouli alcohol(PA) and pogostone(PO) have a high medicinal value by virtue of anti-tumor, anti-inflammatory, antibacterial, antioxidant, and other biological activities. Due to the low content of terpenoid metabolites in P. cablin, the study of biosynthesis and metabolism regulation can provide a biosynthetic basis for obtaining high-content terpenoids. In this study, key enzyme genes in biosynthesis, transcription factors in metabolism regulation, spatio-temporal expression of terpene synthase were reviewed, aiming to provide a reference for the development, protection, and utilization of P. cablin resources.
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Pogostemon/genética , Terpenos , Fatores de Transcrição/genéticaRESUMO
Objective To establish an artificial intelligence model based on B-mode thyroid ultrasound images to predict central compartment lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC). Methods We retrieved the clinical manifestations and ultrasound images of the tumors in 309 patients with surgical histologically confirmed PTC and treated in the First Medical Center of PLA General Hospital from January to December in 2018.The datasets were split into the training set and the test set.We established a deep learning-based computer-aided model for the diagnosis of CLNM in patients with PTC and then evaluated the diagnosis performance of this model with the test set. Result The accuracy,sensitivity,specificity,and area under receiver operating characteristic curve of our model for predicting CLNM were 80%,76%,83%,and 0.794,respectively. Conclusion Deep learning-based radiomics can be applied in predicting CLNM in patients with PTC and provide a basis for therapeutic regimen selection in clinical practice.
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Humanos , Inteligência Artificial , Linfonodos/diagnóstico por imagem , Metástase Linfática , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagemRESUMO
Trace metals deficiency or excess are associated with the etiology and pathogenesis of rheumatoid arthritis(RA). Aconiti Radix Cocta(A) and Paeoniae Radix Alba(B) are commonly used together for the treatment of RA. In this study, we aim to determine anti-arthritic-related metal bioavailability in the compatibility of herb A and B for avoiding metal deficiency or excess, and optimize the combination ratio of herb A and B, accordingly. Anti-arthritic-related metal bioaccessibility were evaluated by in vitro simulator of all gastrointestinal tract(including mouth, stomach, small and large intestines), and the roles of gastrointestinal digestive enzymes and intestinal microflora were investigated. Anti-arthritic-related metal bioavailability was assessed by the affinity adsorption with liposomes. The results indicated that compatibility proportion of corresponding herbal plants, gastrointestinal digestion and microbial metabolic, which could affect metal digestion and absorption. The optimal compatibility proportion of 1 A∶1 B is recommended, according to the dose of anti-arthritic-related metal bioavailability, which is often chosen for clinical practice of RA therapy. Thus, anti-arthritic-related metal bioavailability might be the key active substances for RA treatment.
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Aconitum , Disponibilidade Biológica , Medicamentos de Ervas Chinesas , PaeoniaRESUMO
To explore the value of trans-rectal shear wave elastic mode combined with elastic modulus in the diagnosis of prostate cancer and establish a new method for the evaluation of prostate with trans-rectal shear wave elastography(SWE). The typical findings of trans-rectal ultrasound(US)and SWE in 79 patients with prostate cancer(=41)and benign prostatic hyperplasia(BPH)(=38)confirmed by surgery or US-guided biopsy were analyzed retrospectively.Their diagnostic value were evaluated with the pathological results as the golden standards. Three or more malignant features detected by conventional trans-rectal US(=42.5,<0.001)and asymmetrical SWE mode(=54.2,<0.001)showed statistically significant difference in prostate cancer and BPH groups.The elastic modulus of Emean and Emax in the prostate cancer group were(92.8±21.5)and(114.2±29.8)kPa,which were significantly higher than those in the BPH group [(56.7±14.0)(=-8.8,<0.001)and(68.4±17.2)kPa(=-8.3,<0.001)].The receiver-operating characteristic(ROC)curve with Logistic regression showed that the elastic model combined elastic modulus had the largest area under ROC curve and the highest diagnosis efficiency of prostate cancer,with the cutoff value of 0.45.The diagnosis sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of the combination were 95.1%,89.5%,90.7%,94.4%,and 92.4%,respectively. Combination of SWE mode and elastic modulus is more valuable than elastic modulus alone in the diagnosis of prostate cancer.
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Objective: To investigate the predictive value of N-terminal type B natriuretic peptide(NT-proBNP) on the prognosis of elderly hospitalized patients without heart failure(non-heart failure). Method: Elderly patients aged 65 years or older, who were admitted to Beijing Hospital from September 2018 to February 2019, were enrolled in this study. Patients with clinical diagnosis of heart failure or left ventricular ejection fraction(LVEF)<50% were excluded. The patients were divided into 2 groups based on the serum NT-proBNP level: low NT-proBNP group (<125 ng/L) and high NT-proBNP group(≥125 ng/L). Patients were followed up at 3, 6, and 12 months after enrollment, and the major adverse events were recorded. The composite endpoint events included all-cause mortality, readmission or Emergency Department visits. Cardiovascular events include death, readmission or emergency room treatment due to cardiogenic shock, myocardial infarction, angina pectoris, arrhythmia, heart failure or stroke/transient ischemic attack. Results: A total of 600 elderly patients with non-heart failure were included in the analysis. The average age was (74.9±6.5) years, including 304(50.7%) males. The median follow-up time was 344(265, 359) days. One hundred and seventy-eight(29.7%) composite endpoint events were recorded during the follow-up, 19(3.2%) patients died, and 12(2.0%) patients were lost to follow-up. There were 286(47.7%) cases in low NT-proBNP group and 314 cases(52.3%) in high NT-proBNP group. Patients were older, prevalence of atrial fibrillation and myocardial infarction was higher; MMSE scores and ADL scores, albumin and creatinine clearance rate were lower in high NT-proBNP group than in low NT-proBNP group(all P<0.05). At 1-year follow-up, the incidence of composite endpoint events was significantly higher in high NT-proBNP group than in low NT-proBNP group(33.4%(105/314) vs. 24.8%(71/286), P = 0.02). Cardiovascular events were more common in high NT-proBNP group than in low NT-proBNP group(17.5%(55/314) vs. 8.4%(24/286), P = 0.001). Kaplan-Meier survival analysis showed both composite endpoint events(Log-rank P=0.016) and cardiovascular events(Log-rank P=0.001) were higher in high NT-proBNP group than in low NT-proBNP group. All-cause mortality was also significantly higher in highNT-proBNP group than in lowNT-proBNP group(4.8%(15/314) vs. 1.4%(4/286), P = 0.020), and Kaplan-Meier survival analysis demonstrated borderline statistical significance(Log-rank P = 0.052). Cox proportional hazard regression analysis showed that after adjusting for age, sex, creatinine clearance rate, myocardial infarction, and atrial fibrillation, NT-proBNP remained as an independent risk factor for composite endpoint events(HR=1.376,95%CI 1.049-1.806, P=0.021), and cardiovascular events(HR=1.777, 95%CI 1.185-2.664, P=0.005), but not for all-cause mortality(P=0.206). Conclusions: NT-proBNP level at admission has important predictive value on rehospitalization and cardiovascular events for hospitalized elderly non-heart failure patients. NT-proBNP examination is helpful for risk stratification in this patient cohort.
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Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Biomarcadores , Insuficiência Cardíaca , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Volume Sistólico , Função Ventricular EsquerdaRESUMO
OBJECTIVE@#To evaluate and compare whole exome sequencing (WES) and targeted panel sequencing in the clinical molecular diagnosis of the Chinese families affected with inherited retinal dystrophies (IRDs).@*METHODS@#The clinical information of 182 probands affected with IRDs was collected, including their family history and the ophthalmic examination results. Blood samples of all probands and their relatives were collected and genomic DNA was extracted by standard protocols. The first 91 cases were subjected to the WES and the other 91 cases were subjected to a specific hereditary eye disease enrichment panel (HEDEP) designed by us. All likely pathogenic and pathogenic variants in the candidate genes were determined by Sanger sequencing and co-segregation analyses were performed in available family members. Copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation-dependent probe amplification (MLPA). As PRGR ORF15 was difficult to capture by next generation sequencing (NGS), all the samples were subjected to Sanger sequencing for this region. All sequence changes identified by NGS were classified according to the American College of Medical Gene-tics and Genomics and the Association for Molecular Pathology (ACMG/AMP) variant interpretation guidelines. In this study, only variants identified as pathogenic or likely pathogenic were included, while those variants of uncertain significance, likely benign or benign were not included.@*RESULTS@#In 91 cases with WES, pathogenic or likely pathogenic variants were determined in 30 cases, obtaining a detection rate of 33.00% (30/91); While in 91 cases with HEDEP sequencing, pathogenic or likely pathogenic variants were determined in 51 cases, achieving the diagnostic rate of 56.04% (51/91), and totally, the diagnostic rate was 44.51%. HEDEP had better sequencing coverage and read depth than WES, therefore HEDEP had higher detection rate. In addition, HEDEP could detect CNVs. In this study, we detected disease-causing variants in 29 distinct IRD-associated genes, USH2A, ABCA4 and RPGR were the three most common disease-causing genes, and the frequency of these genes in Chinese IRDs population was 11.54% (21/182), 6.59% (12/182) and 3.85% (7/182), respectively. We found 43 novel variants and 6 cases carried variants in RPGR ORF15.@*CONCLUSION@#NGS in conjunction with Sanger sequencing offers a reliable and effective approach for the genetic diagnosis of IRDs, and after evaluating the pros and cons of the two sequencing methods, we conclude that HEDEP should be used as a first-tier test for IRDs patients, WES can be used as a supplementary molecular diagnostic method due to its merit of detecting novel IRD-associated genes if HEDEP or other methods could not detect disease-causing va-riants in reported genes. In addition, our results enriched the mutational spectra of IRDs genes, and our methods paves the way of genetic counselling, family planning and up-coming gene-based therapies for these families.
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Humanos , Variações do Número de Cópias de DNA , Mutação , Linhagem , Distrofias Retinianas/genética , Sequenciamento do ExomaRESUMO
Objective:To investigate the protective effect of gastrin on rat chondrocytes treated with interleukin-1β (IL-1β) and underlying mechanism. Methods:Chondrocytes of knee joint of newborn rats were isolated and cultured. The effect of gastrin on cell viability was determined by MTT assay. In addition, after being induced with 10 ng/mL of IL-1β for 2 d, the chondrocytes were treated with 1×10-7 mol/L of gastrin for 3 d. The expressions of chondrocyte catabolic genes, i.e., matrix metalloproteinase 3 (MMP3) and MMP13, and the key proteins in gastrin-related signaling pathway, i.e., cholecystokinin B receptor (CCKBR), extracellular regulated protein kinases (ERK), phospho-ERK (p-ERK) and p65 were detected by real-time PCR and Western blotting, respectively. Results:Gastrin with the concentration of 1×10-7 mol/L had no cytotoxic effects on the viability of chondrocytes. Based on IL-1β induction, the expressions of MMP3 and MMP13 genes were significantly downregulated by gastrin. Meanwhile, the expression of CCKBR in the IL-1β induction group and gastrin treatment groups was higher than that in the normal control group. Gastrin also facilitated the phosphorylation of ERK and resulted in the inhibition of P65. Conclusion:Gastrin increases the phosphorylation level of ERK by activating its receptor CCKBR, thereby inhibiting the activity of P65 in NF-κB pathway, antagonizing the chondrocyte catabolic activity induced by IL-1β. Accordingly, gastrin may possess the potentials of cartilage matrix protection via inhibiting mRNA expressions of MMP3 and MMP13 and catabolism in rat chondrocytes.
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Objective The aim of this article was to investigate the effect of nasal endoscopic surgery (NES) using low-temperature plasma radiofrequency (LTPRF) in the treatment of juvenile nasopharyngeal angiofibroma (JNA). Methods We retrospectively analyzed the clinical data on 38 cases of JNA treated by NES+LTPRF (n = 26) or conventional surgical resection (control, n = 12) in Drum Tower Hospital of Nanjing University School of Medicine from January 2012 to December 2018. We compared the operative time, postoperative Lund-Mackay endoscopy scores (LMES), incidence of complications, postoperative recovery, rate of recurrence, and Visual Analogue Scale (VAS) scores between the two groups of patients. Results The rates of LMES gradesⅠ and Ⅱ were significantly higher while those of grades Ⅲ and Ⅳ remarkably lower in the NES+LTPRF than in the control group (P < 0.05). Compared with the controls, the patients of the NES+LTPRF group showed markedly shorter time of nasal mucosa epithelialization ([3.5 ± 0.1] vs [2.3 ± 0.1] mo, P < 0.05) and lower rates of postoperative complications (38.5% vs 7.7%, P < 0.05), recurrence (16.7% vs 3.8%, P < 0.05), and VAS scores at 3 days, 2 months, 6 months and 12 months after surgery (P < 0.05). Conclusion NES+LTPRF is an effective strategy for the treatment of juvenile nasopharyngeal angiofibroma and worthy of a wide clinical application.
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Objective·To investigate therapeutic effect of gastrin on steroid-associated osteonecrosis (SAON) in rat model. Methods·Twenty-four SD rats were randomly divided into three groups i.e. normal control group (normal group), SAON control group (SAON group) and SAON treatment group (treatment group). SAON group and treatment group were intravenously injected with lipopolysaccharide 1 time per day (600 μg/kg) for 2 d and meanwhile intramuscularly injected with methylprednisolone 1 time per day (50 mg/kg) for 3 d. Normal group was injected with normal saline of the same volumns. After steroid injections, treatment group was injected with gastrin 1 time per day (800 μg/kg) for 14 d, while SAON group was injected with normal saline of the same volumns. After the treatment, bone trabeculas below femoral head growth plate were dissected in the rats for bone histology. Hematoxylin-eosin (H-E) staining, immunohistochemistry, fluorescence staining and Goldner's trichrome staining were applied in this study. Results·SAON model in rats was successfully established. The result of H-E staining showed that compared with SAON group, thrombus area, number and area of fat cells in the bone marrows of treatment group obviously decreased (all P<0.05). Immunohistochemistry showed that osteogenic transcription factor (Sp7) positive cells in treatment group were more than those in SAON group (P<0.01). Compared with SAON group, osteoid length and area (Goldner′s trichrome staining), and bone formation rate and bone mineralization deposition rate (fluorescence staining) all significantly increased in treatment group (all P<0.01). Conclusion·Gastrin can effectively treat SAON in rats by suppressing thrombus and lipid formation and enhancing bone-formation.
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<p><b>OBJECTIVE</b>To study the reference ranges of six sex hormones, i.e., luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone, for healthy children aged 0-18 years in Shenzhen, China.</p><p><b>METHODS</b>Stratified cluster sampling was performed to select 2 178 healthy children aged 0-18 years in the districts of Futian, Luohu, Nanshan, Bao'an, and Longgang in Shenzhen between September 2015 and September 2016. There were 1 219 boys and 959 girls, including 81 neonates, 335 infants, 346 young children, 469 preschool children, 419 school-aged children, and 528 adolescents. The American Beckman DXI800 chemiluminescence meter was used to measure the levels of luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone.</p><p><b>RESULTS</b>There were significant differences in the levels of luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone between different age groups (P<0.05). There were also significant differences in the levels of these sex hormones between boys and girls in the same age group (P<0.05). The reference ranges of six sex hormones were established for healthy children aged 0-18 years in Shenzhen based on the levels of these hormones in different age groups.</p><p><b>CONCLUSIONS</b>There are significant differences in sex hormones between different age groups or sex groups. The reference ranges of six sex hormones established for different sexes or ages have great significance in the diagnosis and treatment of endocrine diseases in children.</p>
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Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores Etários , Estradiol , Sangue , Hormônio Foliculoestimulante , Sangue , Hormônios Esteroides Gonadais , Sangue , Medições Luminescentes , Hormônio Luteinizante , Sangue , Progesterona , Sangue , Valores de Referência , Testosterona , SangueRESUMO
<p><b>OBJECTIVE</b>To investigate the mechanism by which propofol exposure causes PC12 cell apoptosis under hypoxic conditions.</p><p><b>METHODS</b>PC12 cells were exposed to room air, 35% oxygen, or 5% oxygen (hypoxia) for 24 h in the presence of either 10 µmol/L lipid emulsion or 10 µmol/L propofol. After the treatments, the cell apoptosis was measured by flow ceytometry, and the level of reactive oxygen species (ROS) and the activity of superoxide dismutase (SOD) were evaluated.</p><p><b>RESULTS</b>In room air, PC12 cells treated with propofol showed increased apoptosis rate and ROS production as compared with the cells treated with the lipid emulsion; propofol treatment of the cells exposed to 35% oxygen showed obvious enhancement of the apoptosis rate, ROS production and SOD activity. Under the hypoxic condition, propofol treatment even further increased the apoptosis rate, ROS production and SOD activity. Lipid emulsion caused no such changes in cells exposed to room air, 35% oxygen or 5% oxygen.</p><p><b>CONCLUSION</b>Under hypoxic conditions, propofol can cause apoptosis in PC12 cells by inducing oxidative stress injury.</p>
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Animais , Ratos , Apoptose , Hipóxia Celular , Estresse Oxidativo , Células PC12 , Propofol , Farmacologia , Espécies Reativas de Oxigênio , Metabolismo , Superóxido Dismutase , MetabolismoRESUMO
OBJECTIVE: To establish a method for determining methanol, ethanol and methylene dichloride residues of low molecular weight heparin(LMWH) by gas chromatography.
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<p><b>OBJECTIVE</b>To study environment-friendly determination of azobenzene in trace amounts using beta-cyclodextrin (beta-CD)-modified Au electrode.</p><p><b>METHODS</b>beta-CD-modified Au electrode was fabricated with a two-step approach, and then a gold electrode modified with beta-CD was used to detect azobenzene by employing Osteryoung square wave voltammetry.</p><p><b>RESULTS</b>The modified electrode could detect azobenzene, showing a good linearity between the electrochemical current and concentration.</p><p><b>CONCLUSION</b>Although the electrochemical current is related with concentration, the detection limit is around 1.0 x 10(-10) mol/L. This study may provide a new environment-friendly approach for monitoring water quality.</p>