Objective To investigate the mutations of the gene in Chinese patients with X linked juvenile retinoschisis (XLRS), and to provide the genetic diagnosis and consultation of heredity for the patients and their families. Methods Genomic DNA was isolated from leukocytes of 29 male patients with XLRS, 38 female carriers and 100 normal controls (the patients and the carriers were from 12 families). All 6 exons of XLRS1 gene were amplified by polhism (SSCP) assay. The positions and types of XLRS1 gene mutations were determined by direct sequencing. Results Eleven different XLRS1 mutations were identified in these 12 families, including one frameshift mutation due to base loss of the first exon: c.22delT（L9CfsX20）, one nonsense mutation due to base loss of the first exon (Trp163X), one splice donor site mutation(c.52+2 Trarr;C; IVS1+2T to C), and eight missense mutation due to base replacement（Ser73Pro, Arg102Gln, Asp145His, Arg156Gly, Arg200Cys, Arg209His, Arg213Gln, and Cys223Arg). No gene mutation was detected in the control group. Four new mutations included frmaeshift mutation（L9CfsX20）and mutations of Asp145His, Arg156Gly, and Trp163X at the fifth exon. A newly discovered non-disease-related polymorphism (NSP) was the c.576C to T (Pro192Pro) change at the sixth exon. Conclusion Eleven different XLRS1 mutations were detected, which is the cause of XLRS in Chinese people. The detection of gene mutations may provide the guidance of genetic diagnosis and the consultation of family heredity for the patients and their families. (Chin J Ocul Fundus Dis, 2006, 22: 77-81)
ObjectiveTo explore the echocardiography characteristics of aortic valve disease (AVD) among different ethnic groups in Xinjiang.MethodsThe data of a large sample (n=130 358) of different ethnic groups in Xinjiang based on the results of echocardiography were analyzed between January 2011 and December 2016, and the echocardiography characteristics of AVD among the Han nationality and different ethnic minorities in Xinjiang were summarized.ResultsThe study recruited 130 358 patients, involving Han nationality (58.49%) and 33 ethnic minorities. The ethnic minorities included the Uygur (27.42%), Kazak (7.47%), Hui nationality (3.48%) and other minorities (3.13%). Apart from Uygur, Kazak and Hui nationality, no description was given due to the small sample sizes of other minorities (3.13%). In the total study population, the prevalence of aortic valve stenosis (AS) was 0.44%, and the prevalence of severe AS was 0.10%; the prevalence of aortic valve regurgitation (AR) was 0.37%, and the prevalence of severe AR was 0.02%; the prevalence of aortic valve calcification (AVC) was 6.51%, and the highest AVC prevalence existed in ≥75 years old age group (24.45%); the prevalence of bicuspid aortic valve (BAV) was 0.54%, and the highest BAV prevalence existed in 18-44 years old age group (0.86%). Among different ethnic groups, the Uygur had the highest prevalence in terms of AS (0.60%), AR (0.63%) and BAV (0.88%), while the Han had the lowest prevalence in terms of AS (0.37%) and AR (0.24%), but the highest AVC prevalence existed in the Han nationality (7.83%). The etiology of AVD showed that the degenerative valve changes was the main cause of AS with the largest proportion of 61.97%. While the aorta root diseases (35.97%) and BAV (22.87%) were the main etiology of AR.ConclusionsIn Xinjiang the overall prevalence of AVD is low. In the elderly population, the Uygur, Kazak and Hui nationality have the higher AS prevalence than the Han nationality does. Different ethnic groups have different AVD characteristics based on the echocardiography. In the Uygur group, AVD presents the younger age of onset; the prevalence of BAV is the highest in the Uygur population, while the lowest in the Hui nationality.
Objective To screen pyroptosis-related miRNAs of acute aortic dissection (AAD) from the GEO database, and analyze and verify their functions. MethodsThe microarray data set based on the miRNA chip in the GEO database was downloaded, the differentially expressed miRNAs were screened, and the target genes were predicted by the miRWalk database. Pyroptosis-related genes (PRGs) were searched in the PubMed database with "pyroptosis" as the keyword, and the intersection of PRGs and differential miRNAs predicting target genes were taken as AAD PRGs by Venn diagram. GO and KEGG enrichment analyses were performed. CytoHubba was used to screen the critical AAD PRGs and then the AAD pyroptosis-related miRNAs were identified. Aortic tissues were collected from gender- and age-matched AAD patients and healthy people, and the critical PRGs and miRNAs were verified by Western blotting and RT-qPCR. ResultsA total of 46 AAD differentially expressed miRNAs were screened, and 49 AAD PRGs were obtained by Venn diagram. GO enrichment analysis showed that the genes played a vital role in apoptosis regulated by cysteine endopeptidases. KEGG analysis showed that the genes enriched in Salmonella infection, necroptosis, and Nod-like receptor signaling pathways. CytoHubba screened the critical AAD PRGs such as cysteine aspartase-1 (Caspase-1), tumor necrosis factor (IL)-1β, and tumor necrosis factor (TNF), then obtained 12 AAD pyroptosis-related miRNAs. Aortic tissues were collected from 6 AAD patients and 6 healthy people. There were 5 males and 1 females in the AAD group with an average age of 48.70±6.35 years, and 4 males and 2 females in the healty control group with an average age of 45.30±4.58 years. There was no statistical difference between the two groups in terms of gender, age, smoking history, hypertension, diabetes, or coronary heart disease (P>0.05). Western blotting and RT-qPCR results showed that Caspase-1 was up-regulated in the AAD patients' aortic tissues compared with the healthy aorta, and the corresponding miRNAs were miR-198, miR-3202, and miR-514b-5p, which were all down-regulated. Conclusion Through bioinformatics analysis and verification, the critical AAD PRGs are Caspase-1, IL-1β, and TNF, and Caspase-1 is up-regulated and 3 corresponding pyroptosis-related miRNAs are down-regulated, which provides new ideas for the molecular mechanism and targeted therapy of AAD cell pyroptosis.
ObjectiveTo evaluate the changes in the expression and significance of serum exosomal miRNAs in patients with DeBakey typeⅠacute aortic dissection (AAD). MethodsTwelve male patients with AAD and six healthy male medical examiners from our hospital were retrospectively included in this study. According to the time of chest pain, the AAD patients were divided into an AAD group within 24 h of chest pain onset, aged 47.00±8.79 years and an AAD group within 48 h of chest pain onset, aged 50.17±9.99 years. The healthy males were allocated to a control group, aged 49.17±4.26 years. Serum exosomal miRNAs were isolated, identified and quantified, and then differentially expressed exosomal miRNAs were screened. The bioinformatic analyses such as GO and KEGG were performed on the differentially expressed exosomal miRNAs. ResultsHigh-throughput screening results revealed differential expression of AAD serum exosomal miRNAs. The upregulated miRNAs of AAD groups was hsa-miR-574-5p (P<0.05), and downregulated miRNAs were hsa-miR-223-3p, hsa-miR-146b-5p, hsa-miR-15b-5p, and hsa-miR-155-5p (P<0.05). Further bioinformatic analysis of the above miRNAs revealed that they were mainly enriched in signaling pathways such as transforming growth factor-β, cell cycle and endoplasmic reticulum protein synthesis. ConclusionDifferential expressions of serum exosomal miRNAs in AAD patients may be related to the pathogenesis of AAD, providing new ideas and clues for further exploration of AAD diagnostic markers and pathogenesis.
Objective To assess the effectiveness and safety of different dual antiplatelet therapies in patients undergoing percutaneous coronary intervention. Methods Such databases as The Cochrane Library, MEDLINE, EMbase, CBM, CNKI and WanFang Data were searched to collect the randomized controlled trials (RCTs) and observational studies on the effectiveness and safety of dual antiplatelet therapies both short-duration (≤6 months) and long-duration (gt;6 months) after percutaneous coronary intervention. The literature was screened according to the inclusive and exclusive criteria by two reviewers independently, the quality was evaluated, the data were extracted, and meta-analyses were performed by using RevMan 5.1 software. Results Eight trials were included, of which 3 were RCTs involving 7 475 patients, and 5 were observational studies involving 12 744 patients. Meta-analyses on RCTs showed that the incidence of death or myocardial infarction in the long-duration treatment group was lower than that of the short-duration treatment group (OR=0.74, 95%CI 0.56 to 0.98, Plt;0.000 1), while meta-analyses on observation studies showed the similar result (OR=0.7, 95%CI 0.45 to 1.08, P=0.11). With the variables of published year and follow-up time, the heterogeneity of cohort studies was discussed through meta-regression (Z=3.61, P=0.000) which indicated that both published year and follow-up time might be the source of heterogeneity due to their contribution. For RCTs, the incidence of severe bleeding events in the short-duration treatment group was lower than that in the long-duration treatment group (OR=1.29, 95%CI 0.99 to 1.69, P=0.06). For observational studies, the incidence of late stent thrombosis in the long-duration treatment group was lower than that in the short-duration treatment group (OR=0.40, 95%CI 0.15 to 1.07, P=0.07). Conclusion The long duration (gt;6months) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention can reduce the incidence of death or myocardial infarction and decrease the tendency of late stent thrombosis, but cannot obviously increase the incidence rate of severe bleeding events. The current evidence shows no marked superiority in longer duration (gt;12months) of dual antiplatelet therapy.
Objective To determine the benefits of an invasive compared to a conservative strategy for treating unstable anguba (UA)/ non-ST-elevation myocardial infarction (NSTEMI). Methods We searched The Cochrane Library (Issue 4, 2009), MEDLINE (1996 to September 2009), EMbase (1974 to September 2009), CBM (1989 to 2009), CNKI (1997 to 2009), and VIP (1989 to 2009). The quality of the included studies was critically evaluated. Data analyses were performed using the Cochrane Collaboration’s RevMan 5.0 software. Results Seven randomized controlled trials involving 11 394 patients met the inclusion criteria. The results meta-analyses showed the incidence of all-cause mortality at six months follow-up was lower in the early invasive group compared with the conservative group (RR=0.75, 95%CI 0.61 to 0.92, P=0.007); the relative risk of myocardial infarction was significantly decreased in the early invasive group (RR=0.74, 95%CI 0.63 to 0.87); there was a reduction in rehospitalization for unstable angina in the invasive group (RR=0.66, 95%CI 0.61 to 0.73, Plt;0.000 01); the invasive strategy was associated with a two-fold increase in the relative risk of PCI-related myocardial infarction (as variably defined). There was not a significant increase in bleeding by an invasive strategy at six months follow-up, but, a routine invasive strategy was associated with a significantly higher bleeding rate at 1-year follow-up (RR=2.22, 95%CI 1.55 to 3.17, Plt;0.000 1). Patients with elevated cardiac biomarker levels at baseline benefited more from routine intervention, with no significant benefit observed in patients with negative baseline marker levels. Conclusion An early invasive strategy is preferable to a conservative strategy in the treatment of UA/NSTEMI, especially higher-risk patients with elevated cardiac biomarker benefit more from invasive strategy. In addition, complications such as procedure-MI and bleeding must be paid great attention to.
Objective To systematically review the efficacy and safety of different duration of dual antiplatelet therapies in patients undergoing new-generation drug-eluting stents implantation. Methods Such databases as MEDLINE, The Cochrane Library (Issue 2, 2015), EMbase, CBM, CNKI and WanFang Data were searched to collect studies on the different duration of dual antiplatelet therapies in patients undergoing new-generation drug-eluting stents implantation from inception to April 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results Six trials were included. The results of meta-analysis showed: compared with 12 months dual antiplatelet therapy group, the incidence of bleeding in the 6 months dual antiplatelet therapy group was lower (OR=0.48, 95%CI 0.26 to 0.89, P=0.02). There were no significant differences in incidence of myocardial infarction, all cause mortality, stroke and stent thrombosis between two groups. Compared with 24 months dual antiplatelet therapy group, the incidence of stent thrombosis in the 12 months dual antiplatelet therapy group was higher (OR=2.50, 95%CI 1.13 to 5.61, P=0.02), but the incidence of bleeding in 12 months dual antiplatelet therapy group was lower (OR=0.25, 95%CI 0.07 to 0.89, P=0.03). No significant differences were found in the incidence of myocardial infarction, all cause mortality and stroke between 12 months dual antiplatelet therapy group and 24 months dual antiplatelet therapy group. Conclusions 6 months dual antiplatelet therapy following new-generation drug-eluting stent implantation is relatively more safe and efficacy. There is significant increase of incidence of bleeding in 12 or 24 months dual antiplatelet therapy. Due to the limited quantity and quality of included studies, the above results are needed to be validated by more high quality studies.
ObjectiveTo analyze the R0 resection rate and survival time of pancreatic cancer with serum IgG4 elevated, and to discuss whether serum IgG4 can distinguish autoimmune pancreatitis from pancreatic cancer.MethodsThe retrospective cohort study was adopted. The clinical data of 146 patients with pancreatic cancer confirmed by histology in Affiliated Hospital of Qingdao University from January 2016 to December 2019 were analyzed retrospectively. According to the level of serum IgG4, they were divided into normal IgG4 group (<1.35 g/L, n=124) and IgG4 elevated group (≥1.35 g/L, n=22). The tumor R0 resection rate, survival time and whether complicated with AIP of the two groups were compared.ResultsOne hundred and one patients (81.5%) with normal serum IgG4 underwent radical surgery, while only 13 patients (59.1%) with elevated serum IgG4 underwent radical surgery, the difference was significant (P=0.019). The median survival time of patients with normal serum IgG4 was 18.7 months, while patients with elevated serum IgG4 was 8.1 months, there was no significant difference between the two groups (P=0.121). Subgroup analysis showed that the median survival time of patients with pancreatic ductal adenocarcinoma in the normal IgG4 group was 17.5 months, while the IgG4 elevated group was 6.8 months, the difference was significant (P=0.016). Only 1 case of pancreatic cancer with AIP in the 2 groups.ConclusionsSerum IgG4 ≥1.35 g/L indicates low radical resection rate in pancreatic cancer and poor prognosis in pancreatic ductal adenocarcinoma. Serum IgG4 can only be used as an auxiliary index to distinguish pancreatic cancer from autoimmune pancreatitis.
Objective To evaluate the clinical radiological features combined with circulating tumor cells (CTCs) in the diagnosis of invasiveness evaluation of subsolid nodules in lung cancers. Methods Clinical data of 296 patients from the First Hospital of Lanzhou University between February 2019 and February 2021 were retrospectively included. There were 130 males and 166 females with a median age of 62.00 years. Patients were randomly divided into a training set and an internal validation set with a ratio of 3 : 1 by random number table method. The patients were divided into two groups: a preinvasive lesion group (atypical adenomatoid hyperplasia and adenocarcinoma in situ) and an invasive lesion group (microinvasive adenocarcinoma and invasive adenocarcinoma). Independent risk factors were selected by regression analysis of training set and a Nomogram prediction model was constructed. The accuracy and consistency of the model were verified by the receiver operating characteristic curve and calibration curve respectively. Subgroup analysis was conducted on nodules with different diameters to further verify the performance of the model. Specific performance metrics, including sensitivity, specificity, positive predictive value, negative predictive value and accuracy at the threshold were calculated. Results Independent risk factors selected by regression analysis for subsolid nodules were age, CTCs level, nodular nature, lobulation and spiculation. The Nomogram prediction mode provided an area under the curve (AUC) of 0.914 (0.872, 0.956), outperforming clinical radiological features model AUC [0.856 (0.794, 0.917), P=0.003] and CTCs AUC [0.750 (0.675, 0.825), P=0.001] in training set. C-index was 0.914, 0.894 and corrected C-index was 0.902, 0.843 in training set and internal validation set, respectively. The AUC of the prediction model in training set was 0.902 (0.848, 0.955), 0.913 (0.860, 0.966) and 0.873 (0.730, 1.000) for nodule diameter of 5-20 mm, 10-20 mm and 21-30 mm, respectively. Conclusion The prediction model in this study has better diagnostic value, and is more effective in clinical diagnosis of diseases.
ObjectiveTo establish a machine learning model based on computed tomography (CT) radiomics for preoperatively predicting invasive degree of lung ground-glass nodules (GGNs). MethodsWe retrospectively analyzed the clinical data of GGNs patients whose solid component less than 3 cm in the Department of Thoracic Surgery of Shanghai Pulmonary Hospital from March 2021 to July 2021 and the First Hospital of Lanzhou University from January 2019 to May 2022. The lesions were divided into pre-invasiveness and invasiveness according to postoperative pathological results, and the patients were randomly divided into a training set and a test set in a ratio of 7∶3. Radiomic features (1 317) were extracted from CT images of each patient, the max-relevance and min-redundancy (mRMR) was used to screen the top 100 features with the most relevant categories, least absolute shrinkage and selection operator (LASSO) was used to select radiomic features, and the support vector machine (SVM) classifier was used to establish the prediction model. We calculated the area under the curve (AUC), sensitivity, specificity, accuracy, negative predictive value, positive predictive value to evaluate the performance of the model, drawing calibration and decision curves of the prediction model to evaluate the accuracy and clinical benefit of the model, analyzed the performance in the training set and subgroups with different nodule diameters, and compared the prediction performance of this model with Mayo and Brock models. Two primary thoracic surgeons were required to evaluate the invasiveness of GGNs to investigate the clinical utility of the model. ResultsA total of 400 patients were divided into the training set (n=280) and the test set (n=120) according to the admission criteria. There were 267 females and 133 males with an average age of 52.4±12.7 years. Finally, 8 radiomic features were screened out from the training set data to build SVM model. The AUC, sensitivity and specificity of the model in the training and test sets were 0.91, 0.89, 0.75 and 0.86, 0.92, 0.60, respectively. The model showed good prediction performance in the training set 0-10 mm, 10-20 mm and the test set 0-10 mm, 10-20 mm subgroups, with AUC values of 0.82, 0.88, 0.84, 0.72, respectively. The AUC of SVM model was significantly better than that of Mayo model (0.73) and Brock model (0.73). With the help of this model, the AUC value, sensitivity, specificity and accuracy of thoracic surgeons A and B in distinguishing invasive or non-invasive adenocarcinoma were significantly improved. ConclusionThe SVM model based on radiomics is helpful to distinguish non-invasive lesions from invasive lesions, and has stable predictive performance for GGNs of different sizes and has better prediction performance than Mayo and Brock models. It can help clinicians to more accurately judge the invasiveness of GGNs, to make more appropriate diagnosis and treatment decisions, and achieve accurate treatment.