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Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.
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Ferroptosis is a novel regulatory cell death characterized by iron dependence and mainly caused by the accumulation of lipid peroxides and reactive oxygen species in the cell. This process plays an important role in the development of many malignancies, and has been extensively studied in lung cancer, especially in antitumor therapy. In recent years, the role of ferroptosis in tumor immunotherapy has been gradually explored. Studies showed that targeting ferroptosis can improve the therapeutic efficacy of antitumor immunotherapy. In addition, immunotherapy and ferroptosis can work synergistically to enhance the effectiveness of antitumor therapy, suggesting a potential relationship between ferroptosis and immunotherapy and the possible reversal of immune drug resistance. This study aims to elucidate the characteristics of ferroptosis, and the role and potential clinical applications of ferroptosis in the antitumor immunotherapy of advanced non-small cell lung cancer. We also explore the role of some nanomaterials that target the onset of tumor ferroptosis in facilitating immunotherapy.
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Objective:To establish an evaluation index system for the refinement management of respiratory specialties in four dimensions: medical care, teaching, scientific research and personnel training, to develop a refinement management system based on medical big data, and evaluate the effectiveness of its application.Methods:Based on evaluation indexes and literature of several domestic respiratory specialty influence rankings, an index system covering four dimensions (primary indexes), 16 secondary indexes and 73 tertiary indexes covering medical treatment (30%), teaching (15%), scientific research (40%) and personnel training (15%) was devised using brainstorming, Delphi, and hierarchical entropy weighting. Data from 13 professional groups and 248 respiratory discipline members integrated by the system in 2018 and 2019 were statistically analyzed using the refined index system embedded in the system to understand the system's application after a year of use with comparing the four dimensions of the discipline and the changes among specialty groups before and after implementation.Results:In 2019, respiratory medicine′s comprehensive score grew 30% compared to 2018. The subscores also grew, with scientific research showing the largest growth rate of 136% and talent cultivation showing the second highest. In 2019, ten of the 13 professional groups grew by 2% to 135%.Conclusions:An improved management system for respiratory medicine based on big data technology has provided a comprehensive, intuitive and quantitative view of the discipline′s development in four dimensions and the differences among specialty groups. It will be an effective decision-making tool for ensuring high-quality and balanced discipline development.
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Objective:To analyze the genetic etiology of idiopathic short stature(ISS) children, and to investigate the clinical characteristics of Noonan syndrome caused by PTPN11 gene mutation, and the response to recombinant human growth hormone(rhGH) as well.Methods:Genomic DNA was extracted from the peripheral blood of 232 ISS patients, and the genome was detected by whole exon sequencing. The gene variation was analyzed according to the guideline of American College of Medical Genetics and Genomics(ACMG), and clinical baseline data and follow-up data of rhGH treatment were collected from PTPN11 gene pathogenic patients.Results:Among 232 ISS patients, 6 were found to have PTPN11 pathogenic gene variants(c.1507G>C, c. 317A>G, c. 923A>G, c. 922A>G, c. 236A>G, c. 922A>G), diagnosed as Noonan syndrome. Together with 3 cases of Noonan syndrome patients(all PTPN11 gene variation C. 1510A>G) previously diagnosed in our hospital, the clinical characteristics of patients were analyzed. Among the 9 Noonan syndrome patients, 7 were boys and 2 were girls. The average age was 10.2(4.5, 14.7) years old, and their height standard deviation score was -3.06 SD(95% CI -2.29 SD--3.94 SD). Among them, 4 patients received rhGH treatment with an average treatment duration of 2.25(1.5, 3.5) years. After treatment, their height increased by 14.3(8.6, 23.9) cm, and the change in height standard deviation score improved by 0.21 SD(95% CI 0.12 SD-0.27 SD). Conclusion:Noonan syndrome has a wide range of clinical phenotypes. For children with short stature, heart defects and cryptorchidism, the possibility of Noonan syndrome should be considered. PTPN11 is the common pathogenic gene for Noonan syndrome, and genetic testing facilitates the early diagnosis, treatment, and follow-up prognosis of Noonan syndrome patients.
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Objective:To investigate the association between age and cardiac tamponade after radiofrequency ablation of atrial fibrillation(RAAF).Methods:Clinical data of patients undergone de novo AF ablation procedures at Beijing Anzhen Hospital from January 2013 to December 2016 were retrospectively collected.Patients were divided into an elderly group(age ≥60 years)and a non-elderly group(age <60 years). Logistic regression analyses were used to evaluate the association between old age and the risk of cardiac tamponade complicating RAAF.Results:A total of 5 313 patients were involved in this study, including 41 patients(0.77%)with cardiac tamponade.The proportion of cardiac tamponade was higher in the elderly group than in the non-elderly group(1.1% or 32/2 950 vs.0.4% or 9/2 363, χ2=8.489, P=0.004). One patient with cardiac tamponade in the elderly group required immediate surgical repair whereas none in the non-elderly group did.No patient died in hospital.Multivariate Logistic regression analysis showed that the risk of cardiac tamponade increased in the elderly group, compared with the non-elderly group( OR=2.570, 95% CI: 1.190-5.570, P=0.017). Stratified analysis revealed that among females and patients with oral anticoagulants, left atrium dimension < 40 mm or procedure duration≥ 120 min in the elderly group carried a higher risk of cardiac tamponade than those in the non-elderly group( OR=1.011, 2.914, 3.922 and 3.244, P<0.05). Conclusions:Old age(age ≥60 years)is an independent risk factor for cardiac tamponade complicating RAAF.
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Objective:To study the effects of radiotherapy and the prognostic factors in hepatocellular cancer (HCC) patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis (LNM).Methods:We retrospectively analyzed 56 HCC patients with cardiophrenic angle or superior diaphragmatic LNM who were treated with or without external beam radiation therapy (EBRT) in Zhongshan Hospital of Fudan University from Jan 2010 to Aug 2020. Patients were divided into two groups according to whether they received radiotherapy, EBRT group and non-EBRT group, and each group had 28 patients. Radiation fields included or excluded primary tumor in EBRT group, and the cardiophrenic angle or superior diaphragmatic LNM did not receive any local treatment in non-EBRT group. The response rate, survival rate, local control rate, prognostic risk factors of the two groups were studied.Results:After EBRT, the partial response rate and complete response rate were 32.1%(9/28) and 32.1%(9/28). The median survival rate of EBRT group was 16.1 months (95% CI 9.00-23.21, RR=3.63) vs. 6.9 months (95% CI 4.63-8.77, RR=1.06) for the non-EBRT group, with statistically significant difference ( χ2=15.53, P<0.05). Cardiophrenic angle or superior diaphragmatic lymph nodes 1-year local control rate for EBRT group and non-EBRT group were 37.0% vs. 10.7%, with statistically significant difference ( χ2=5.28, P<0.05). Since diagnosis of cardiophrenic angle or superior diaphragmatic LNM, 4 patients (14.3%) in the EBRT group vs. 13 patients (46.4%) in the non-EBRT group had higher alpha-fetoprotein (AFP) level after 3 months compared with the AFP before EBRT ( χ2=6.84, P<0.05). Multivariate analysis showed that multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L, no EBRT were poor prognostic factors. Conclusions:EBRT can prolong overall survival and improve the control rate of lymph node of HCC patients with cardiophrenic angle or superior diaphragmatic LNM. Patients with multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L and no EBRT have poor prognosis.
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The aim of this study is to o explore the diagnosis, treatment and prognosis of idiopathic subglottic stenosis （ISS） The clinical data of 15 patients with idiopathic subglottic stenosis treated in our department were analyzed retrospectively. The degree of stenosis was classified by the Cotton Airway grading system of Myer, with 8 cases of gradeⅡ, 4 cases of grade Ⅲ and 3 cases of grade Ⅳ. The time of follow-up of HTSS was 0.5-10 years. All 15 patients were successfully extubated without asphyxia, decannulation and wound nonunion. For patients with idiopathic subglottic stenosis in the non-progressive stage, active surgical treatment strategy should be adopted and treated individually. The prognosis is satisfactory.
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Objective:To analyze the clinical characteristics of hereditary neuralgic amyotrophy caused by SEPT9 gene mutation in a family to promote understanding this disease.Methods:The clinical manifestations, examination, imaging and electrophysiology of a family with hereditary neuralgic amyotrophy diagnosed by gene testing in the 960th Hospital of People′s Liberation Army in August 2013 were retrospectively analyzed.Results:The age of the onset ranged from children to middle-aged. The parent-child couples demonstrated the existence of marked anticipation, with earlier age of onset in successive generations. Male and female were involved. The forearm had circular skin creases at a young age. The sudden upper limb pain and weakness were first symptoms, the distal upper limb muscle weakness was more obvious than the proximal, and the wrist was saggy. The course was described as relapsing-remitting, and there were sufficient laxity of the skin and generalized muscle wasting. The cerebrospinal fluid examination and magnetic resonance examination of brachial plexus nerve were normal. The electrophysiology was limited to the peripheral nerve damage of the double upper limbs.Conclusions:Relapsing-remitting focal brachial plexus pain and weakness are the main manifestations of hereditary neuralgic amyotrophy, and the laxity of the skin and generalized thin muscle appear on sequel stage of the clinical repeated attack. The electrophysiological lesion is limited to brachial plexus nerve.
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Objective:To investigate the association between single nucleotide polymorphism (SNP) of eukaryotic translation initiation factor 2-α kinase 3 (EIF2AK3) gene in growth hormone deficiency (GHD), and to determine whether the polymorphisms in the EIF2AK3 of children with GHD associate with the efficacy of recombinant human growth hormone (rhGH) therapy.Methods:Five SNPs of EIF2AK3 gene, including rs1805165 (G>T), rs13045 (A>G), rs867529 (C>G), rs11684404 (T>C), rs6547787(T>G) were selected and genotyped by a TaqMan probe method in 104 children with GHD and 269 normal height control children. Among them, 55 children with GHD were treated with rhGH. The height and weight of each patient with GHD after rhGH treatment were collected. Finally, to investigate whether there were differences between the efficacy of rhGH in children with GHD and different genotypes of EIF2AK3 gene polymorphism.Results:(1) The polymorphisms rs13045 and rs867529 of EIF2AK3 gene were associated with the occurrence of GHD ( P<0.05). (2) The haplotypes GACTG and GAGTT composed of SNPs rs1805165, rs13045, rs867529, rs11684404, and rs6547787 of EIF2AK3 gene increased the risk of GHD with OR (95% CI) of 2.05 (1.33-3.17) and 2.62 (1.48-4.65), respectively. The haplotypes GACTT and TGCCG reduced the risk of GHD, with OR (95% CI) of 0.68 (0.48-0.97) and 0.36 (0.23-0.57), respectively. (3) After determination the relationship between different genotypes and efficacy of rhGH with rs13045 and rs867529, it was found that there was no significant difference in height gain between rs13045 genotypes after rhGH treatment ( P>0.05). Compared with CC genotype, there was a less height gain of CG genotype at rs867529 by 0.099 cm for every 30 d( β=-0.099, 95% CI -0.162--0.018, P=0.016). Conclusions:The EIF2AK3 gene polymorphism (rs13045, rs867529) was associated with the occurrence of GHD. The height gain of CG genotype of rs867529 was lower than that of CC genotype in children with GHD treated with rhGH. The EIF2AK3 locus rs867529 genotype was associated with rhGH efficacy.
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Objective@#The aim of this study is to o explore the diagnosis, treatment and prognosis of idiopathic subglottic stenosis （ISS） @*Method@#The clinical data of 15 patients with idiopathic subglottic stenosis treated in our department were analyzed retrospectively. The degree of stenosis was classified by the Cotton Airway grading system of Myer, with 8 cases of gradeⅡ, 4 cases of grade Ⅲ and 3 cases of grade Ⅳ. @*Result@#The time of follow-up of HTSS was 0.5-10 years. All 15 patients were successfully extubated without asphyxia, decannulation and wound nonunion. @*Conclusion@#For patients with idiopathic subglottic stenosis in the non-progressive stage, active surgical treatment strategy should be adopted and treated individually. The prognosis is satisfactory.
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Objective To perform bioinformatics analysis of the genetic chip data of rheumatoid arthritis (RA) in order to search for the characteristic gene expression profiles. Methods Differential expression analysis of RA Gene chip data in GEO database was performed using GEO2R, and GO and KEGG enrichment analysis of functional annotation and pathway analysis of differentially expressed genes (DEGs) were conducted by DAVID6.8 and R language. Protein-protein interaction (PPI) and target genes acquisition were realized by String-database and software Cytoscape3.7.1. Results The 1 184 DEGs in synovial tissues isolated from the knee joints of RA patients were statistically significant. Among them 664 were up-regulated and 520 were down-regulated. DEGs were enriched to 70 different GOterms, and the most significant terms were signal transduction, plasma membrane and protein binding. DEGs were enriched to 62 different signal pathways, including cytokine-cytokine receptor interaction, osteoclast differentiation, rheumatoid arthritis, Th17 cell differentiation, and IL17 signal pathway. PPI analysis screened out 19 pivotal target genes, namely, NKG7, BCL6, SEMA4D, NFIL3, RAC2, MLIP, SEL1L3, GUSBP11, IGLV1-44, IGLJ3, IGLC1, IGKV1OR2-118, IGKV1OR2-108, IGKC, IGHV4-31, IGHV3-23, IGHM, IGHD and CYAT1. Conclusion Partial DEGs screened out by analyzing the expression profiles are involved in the key links affecting the development of synovial inflammation in RA, which may provide an important theoretical basis for early diagnosis and treatment of this disease and development of targeted drugs.
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Objective To promote the building of the hospital mobile applications architecture in a scientific,user-centered,and needs-oriented way.Methods Function points from mobile applications were rounded up for classification and ranking by means of Kano model and double factor questionnaire survey,for the purpose of qualitative and quantitative analysis of 12 hospitals and identifying the core needs of patients.Statistical methods such as descriptive analysis were used to analyze the data.Results 16 function points of mobile applications were rounded up from 12 hospitals,finding that 12 of their 16 App functions were located in the upper half of the quartile graph,namely appointment and result inquiry.These 12 functions if well met will upgrade patient satisfaction.Conclusions High focus on mobile applications is imperative to upgrade hospital's intelligent medical services,improve the medical efficiency and satisfaction.
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Objective To investigate the independent association of the body mass index(BMI) with serum uric acid among shorter children and adolescent. Methods A cross-sectional study was conducted to collect general clinical data of 922 subjects with shorter statures. In each case, their information about height, weight, insulin-like growth factor-Ⅰ(IGF-Ⅰ), growth hormone peak, uric acid, and blood lipids were collected, and their BMI and BMI standard deviations score( SDS) were calculated. Smooth curve fitting and multiple piecewise linear regression were used to analyze the relationship between BMI SDS and uric acid. Results Univariate analysis found that serum uric acid was positively correlated with age, height standard deviation score, body weight standard deviation score, BMI SDS, IGF-Ⅰ standard deviation score, growth hormone peak, triglyceride, and creatinine ( P＜0. 05 ), while negatively correlated with high-density lipoprotein-cholesterol( P＜0.01). Female had significantly lower serum uric acid levels than male(P=0.003). The serum uric acid level was significantly increased after puberty(P＜0.01). After adjusting for potential confounders, the smooth curve fitting revealed a U-shaped relationship between BMI SDS and uric acid, with a BMI SDS inflection point of-0.7. In the population of BMI SDS＜-0.7, for every unit increase of BMI SDS, serum uric acid decreased by 11. 78 μmol/L( P=0. 030). In the population of BMI SDS≥-0. 7, uric acid increased by 11.79 μmol/L(P＜0.01) for every unit increase of BMI SDS. Conclusion Serum uric acid levels seem to be affected by BMI, and increased in population with thin or obesity. We should pay attention to the measurement of serum uric acid in both thin and obese children.
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Current pharmaceutical formulation development still strongly relies on the traditional trial-and-error methods of pharmaceutical scientists. This approach is laborious, time-consuming and costly. Recently, deep learning has been widely applied in many challenging domains because of its important capability of automatic feature extraction. The aim of the present research is to apply deep learning methods to predict pharmaceutical formulations. In this paper, two types of dosage forms were chosen as model systems. Evaluation criteria suitable for pharmaceutics were applied to assess the performance of the models. Moreover, an automatic dataset selection algorithm was developed for selecting the representative data as validation and test datasets. Six machine learning methods were compared with deep learning. Results showed that the accuracies of both two deep neural networks were above 80% and higher than other machine learning models; the latter showed good prediction of pharmaceutical formulations. In summary, deep learning employing an automatic data splitting algorithm and the evaluation criteria suitable for pharmaceutical formulation data was developed for the prediction of pharmaceutical formulations for the first time. The cross-disciplinary integration of pharmaceutics and artificial intelligence may shift the paradigm of pharmaceutical research from experience-dependent studies to data-driven methodologies.
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Objective To investigate the efficacy of arthroscopic synovectomy on refractory knee arthritis complicated with popliteal cyst.Methods Patients diagnosed as rheumatoid arthritis (RA) or spondyloarthritis (SPA) with refractory knee arthritis who underwent knee arthroscopic synovectomy in our hospital from 2010 to 2017 were enrolled,including 20 patients (16 RA,4 SpA) with popliteal cyst.Clinical data,RA disease activity score (DAS28),SpA back pain score,etc,were collected to evaluate the efficacy of knee surgery.Results Erythrocyte sedimentation rate (ESR) [58(17,79)mm / 1h vs.19(9,30)mm/1h,P＜ 0.001],C reactive protein (CRP) [3.72(0.92,8.14) mg/L vs.0.85(0.10,3.08) mg/L,P＜0.001],rheumatoid factor [64.6(20.2,193.3) vs.20.5(10.0,58.4),P＜0.001],DAS28 score(4.67±1.25 vs.2.81±1.23,P＜0.001),knee joint discomfort score [5(4,6) vs.2(1,3),P＜0.001] and the volume of knee joint effusion by ultrasound (P＜0.05) in 95 RA patients were significantly decreased compared to those before operation.ESR [27(12,54)mm/1h vs.20 (16,28) mm/1 h,P＜0.001],CRP [3.27(1.06,6.95) mg/L vs.1.41(0.34,3.03)mg/L,P＜0.001],knee discomfort score [2(0,5) vs.1(0,3),P＜0.05],back pain visual analogue score (VAS) [5(4,5) vs.2(1,3),P＜0.001],and the volume of knee joint effusion by ultrasound (P＜0.001) in 58 SpA patients were significantly lower than those before the operation.The rate [16.84％(16/95) vs.6.32％(6/95),P=0.023] and grading (P=0.007) of popliteal cyst in RA were decreased after the operation.No statistically difference was observed in the rate [6.90％ (4/58) vs.5.17％(3/58),P=0.697] of popliteal cyst in patients with SpA,yet with a trend of decrease in 4 patients.Conclusion This study provide evidence that knee arthroscopic synovectomy has a good effect for refractory knee arthritis,which can reduce disease activity,improve joint symptoms and decrease the grading of popliteal cyst.
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Most pharmaceutical formulation developments are complex and ideal formulations are generally obtained after extensive experimentation. Machine learning is increasingly advancing many aspects in modern society and has achieved significant success in multiple subjects. Current research demonstrated that machine learning can be adopted to build up high-accurate predictive models in drugs/cyclodextrins (CDs) systems. Molecular descriptors of compounds and experimental conditions were employed as inputs, while complexation free energy as outputs. Results showed that the light gradient boosting machine provided significantly improved predictive performance over random forest and deep learning. The mean absolute error was 1.38 kJ/mol and squared correlation coefficient was 0.86. The evaluation of relative importance of molecular descriptors further demonstrated the key factors affecting molecular interactions in drugs/CD systems. In the specific ketoprofen-CD systems, machine learning model showed better predictive performance than molecular modeling calculation, while molecular simulation could provide structural, dynamic and energetic information. The integration of machine learning and molecular simulation could produce synergistic effect for interpreting and predicting pharmaceutical formulations. In conclusion, the developed predictive models were able to quickly and accurately predict the solubilizing capacity of CD systems. Current research has taken an important step toward the application of machine learning in pharmaceutical formulation design.
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With the aggravation of aging and the increasing demand of the elderly for pension and medical services,the old-age model of medical care combined with nursing emerges as the times required.Traditional Chinese medicine medical institutions have the advantages and opportunities in the process of developing integrated medical and nursing services,such as the treatment and prevention of chronic diseases,the increasing demand of the elderly for integrated medical and nursing institutions,and the strong support of the state for integrated medical and nursing institutions.However,they are also facing challenges and difficulties such as imperfect team,weak market competition and low payment ability.Through the analysis of opportunities and challenges for TCM medical institutions,this paper provides corresponding counter measures and suggestions for their development.
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Objective To systematically review the clinical efficacy and safety of early use of recombinant human erythropoietin (rHu-EPO) for neuroprotection in premature infants.Method From establishment of the databases to November 2017,clinical randomized controlled trials (RCTs) of early use of rHu-EPO in premature infants were searched on English databases (PubMed,Embase,Cochrane Collaboration) and Chinese databases (CNKI,SinoMed,Wanfang,and VIP Database).Patients receiving conventional therapy were assigned into control group,and patients receiving both conventional therapy and rHu-EPO were assigned into rHu-EPO group.rHu-EPO group was subdivided into high-dose continuous group and low-dose intermittent group.We retrieved the related literatures,evaluated the quality,and then performed Meta-analysis using RevMan 5.3 software.Result A total of 2 588 patients in 17 studies were included and analyzed.Compared with the control group,Meta-analysis showed that early use of rHu-EPO was more effective in improving NBNA scores at 40 weeks of corrected gestational age (cGA) (MD=2.46,95％CI 1.58～3.33,P＜0.001),and high-dose continuous group was better than low-dose intermittent group (MD=3.19,95％CI 0.45～5.93,P=0.002;MD=2.22,95％CI 1.29～3.16,P＜0.001).Low-dose intermittent use of rHu-EPO significantly increased mental development index (MDI) (MD=6.66,95％CI 0.80～12.51,P=0.010) and psychomotor development index (PDI) (MD=5.77,95％CI 4.00～7.55,P＜0.001),and reduced the incidence of MDI＜70 at cGA 18～22 months (OR=0.42,95％CI 0.27～0.67,P＜0.001).As to the safety and side effects,treatment with rHu-EPO reduced the risk of necrotizing enterocolitis (OR=0.48,95％CI 0.31 ～0.72,P＜0.001) and periventricular leukomalacia (OR=0.52,95％CI 0.35～0.75,P＜0.001)without increasing the risk of bronchial dysplasia,patent ductus arteriosus,retinopathy in prematurity and intraventricular hemorrhage.Conclusion Current evidence shows that the early use of rHu-EPO in premature infants is relatively effective and safe,but multi-center RCTs are still needed.
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Objective@#To analyze the interpretation results on the pathogenic classification of KCNH2 variants and SCN5A variants of long QT syndrome (LQTS) based on American College of Medical Genetics and Genomics (ACMG) guidelines by 4 clinical gene screening agencies from Beijing.@*Methods@#Pathogenic classification of 16 variants in KCNH2 and SCN5A was made by 4 clinical gene screening agencies from Beijing based on ACMG guideline. Krippendorff's alpha was used to assess the inter-agency variation consistency.@*Results@#All 4 agencies made pathogenic assessment on all the variants and provided the interpretation results for the classification. For the eight variants from the patients with LQTS, the consistency of classification was only 1/8 and the alpha test value was - 0.01. For the eight variables from incidental findings, the consistency of classification was 4/8 and the alpha test value was 0.407. Evidence analysis of the 4 variants with large differences in classification among agencies showed that the main reasons for the discrepancies originated from the comprehensiveness of the literature search and the inconsistency of the subjective determination of the evidence grade.@*Conclusion@#The consistency of the pathogenic classification of LQTS gene variants based on ACMG guidelines among clinical gene screening agencies from Beijing is poor, which will result in great impact on the clinical treatment strategies of the patients with LQTS. The standardization of pathogenic evaluation of variants in clinical gene screening agencies needs to be improved urgently.
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Objective To investigate associations of herpes simplex virus(HSV)infection with elevated high-sensitivity C-reactive protein(hsCRP)level and the development of atrial fibrillation(AF) in elderly individuals.Methods Through screening a total of 2,603 individuals,49 patients aged 60 years or over with AF and without structural heart diseases and known risk factors for AF were selected for data collection.Fifty-five elderly healthy control subjects were selected from a population based Chinese Arrhythmia Registry.Baseline characteristics,plasma antibody levels against HSV-1 and-2,and level of hsCRP were analyzed.Results Level of antibodies against HSV-1 was significantly higher in AF patients[(314.5±63.6)mg/L than in control subjects(216.0±50.7) mg/L,P＜0.01].Level of antibodies against HSV-2 was significantly higher in AF patients[(400.1±50.7) mg/L than in control subjects (306.3 ± 64.5) mg/L,P ＜ 0.01].Linear regression analysis demonstrated a positive correlation of plasma levels of hsCRP with both anti-HSV-1 and anti-HSV-2 IgG antibodies (r =0.291,0.188,all P ＜ 0.01).In multiple logistic regression analysis,HSV-1 and HSV-2 antibody levels were significantly associated with AF occurrence(OR =1.035 and 1.034,all P ＜0.01).The optimal cut-off point for predicting AF occurrence was 284.96 mg/L for anti-HSV-1 with sensitivity of 67.3％ and a specificity of 92.7％,and was 366.26 mg/L for anti-HSV-2 with a sensitivity of 67.3％ and a specificity of 85.5％,respectively.Conclusions The increased plasma levels of anti-HSV-1 and anti-HSV-2 antibodies are significantly associated with AF occurrence in elderly adults.