A radiomics prognostic scoring system for predicting progression-free survival in patients with stageⅣnon-small cell lung cancer treated with platinum-based chemotherapy

Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.

Analysis on Causes of Rural Land Expropriation Disputes Based on Smith's Model

Frequent occurrence of land expropriation disputes in rural areas of China has attracted attention of scholars to study causes. Most existing studies discuss causes from " structure- institution" level. In other words,land expropriation disputes are caused by existing imperfect institutions,regulations,and policies. Such analysis model points institutional causes,but pays little attention to policy implementation process,especially the subjective initiative of parties concerned. This paper described a decade-long land expropriation dispute case in detail.Through description of event and process and survey of reasons of actors,it revealed factors resulting in occurrence and upgrade of dispute,and analyzed factors and their interactions with the aid of Smith Process Model.

A Minor New Diterpenoid Alkaloids from the Roots of Delphinium Souliei Franch

A minor new diterpenoid alkaloid, soulidine, was isolated from the roots of DelphiniumSouliei Franch, its structure was established on the basis of spectral evidences.

Waste to treasure:Reutilization of fluid catalytic cracking coke block as photothermal conversion material for water evaporation

This study aims to analyze the coking process and propose an effective method for the reutilization of fluid catalytic cracking(FCC)coke block.Herein,we analyzed the basic characteristics and chemical composition of FCC coke blocks.The results showed that the main components were carbon,oxygen,and aluminum,accounting for 60.8%,26.6%,and 11.5%,respectively.Under the conventional catalytic cracking reaction temperature from 500℃ to 600℃,the formation of the first aromatic hydrocarbon was particularly important for the formation of coke.The condensation of oil-gas-entrained catalyst particles and their heavy components was the physical cause of coking,while the dehydrogenation condensation reaction of oil-gas heavy components was the chemical factor.In addition,the membrane prepared by powdered coke had excellent photothermal conversion ability,which could be heated to more than 110℃ within 360 s under two fixed light intensities.The evaporation rate of photothermal water was 5.89 kg m^(2) h^(−1),which has great industrial application potential.These works provide a novel and effective method of separation membrane for the reutilization of FCC coke blocks.

基于分子动力学的SiC刀具切削单晶镍刀具磨损分析

通过MD仿真,分析了SiC刀具切削单晶镍,刀具磨损过程中原子的物理化学状态。研究发现,在切削过程中,工件镍原子发生物理移动并与刀具中的硅化学结合;根据径向分布函数分析法以及MD仿真结果,证实了Ni-Si键的生成;切削用量影响这一结果,切削深度越大,刀屑界面的NiSi化合物生成速率越明显,但对最终生成量多少的影响并不显著。而且NiSi化合物硬度低于刀具硬度,随着切深越大,磨损加剧。

84例典型副肿瘤抗体阳性者肿瘤诊断率及肿瘤标志物检测状况分析

目的探讨典型副肿瘤抗体阳性者肿瘤诊断率低下的原因。方法分别用免疫印迹法和电化学发光法检测神经元抗原谱Ig G抗体和肿瘤标志物。通过终末电子病例查询,收集典型副肿瘤抗体(Ig G)阳性者终末诊断、肿瘤标志物检测结果等信息。结果 84例典型副肿瘤抗体阳性者中抗Hu抗体、抗Ri抗体、抗Yo抗体、抗PNMA2(Ma2/Ta)抗体、抗CV2抗体和抗Amphiphysin抗体阳性例数分别为15(17.9%)、0(0.0%)、18(21.4%)、26(31.0%)、9(10.7%)、12(14.3%)例。抗CV2抗体及抗PNMA2(Ma2/Ta)抗体均阳性3例(3.6%),抗CV2抗体及抗Hu抗体均阳性1例(1.2%)。84例典型副肿瘤抗体阳性者的肿瘤诊断率为14.3%,其中抗Amphiphysin抗体阳性、抗Hu抗体阳性者肿瘤诊断率仅为7.4%。72例典型副肿瘤抗体阳性且未诊断为肿瘤的受检者中有14例(19.4%)未进行肿瘤标志物检测,58例行肿瘤标志物检测的受检者中肿瘤标志物结果正常和异常者分别为27例(46.6%)和31例(53.4%)。结论典型副肿瘤抗体阳性者肿瘤漏诊率高,肿瘤标志物漏检、对肿瘤标志物结果正常者进一步探查肿瘤意识不足以及对肿瘤重点探查部位把握不准确等可能是漏诊的主要原因。

纳米级气体静压轴承回转误差测控系统软件开发

基于研制的纳米级气体静压轴承回转误差测试平台,采用C++与Matlab混合编程的方式,设计开发出纳米级气体静压轴承回转误差测控系统软件。该软件可实现运动控制、数据采集、数据处理及结果显示等功能。同时,该软件设计了一种角度误差控制方法,减小了在数据采集过程中引入的角度误差,从而得到了较为准确的主轴回转误差。调试结果表明,测控软件的功能合理,满足主轴回转误差测试精度和技术指标要求,采样角度误差可以控制在±0.01°以内,分离出的标准球圆度误差与标称值(36 nm)的相对误差低于6%。

A CT-based radiomics nomogram for prediction of human epidermal growth factor receptor 2 status in patients with gastric cancer

Objective: To develop and validate a computed tomography(CT)-based radiomics nomogram for predicting human epidermal growth factor receptor 2(HER2) status in patients with gastric cancer.Methods: This retrospective study included 134 patients with gastric cancer(HER2-negative: n=87;HER2-positive: n=47) from April 2013 to March 2018, who were then randomly divided into training(n=94) and validation(n=40) cohorts. Radiomics features were obtained from the CT images showing gastric cancer. Least absolute shrinkage and selection operator(LASSO) regression analysis was utilized for building the radiomics signature. A multivariable logistic regression method was applied to develop a prediction model incorporating the radiomics signature and independent clinicopathologic risk predictors, which were then visualized as a radiomics nomogram. The predictive performance of the nomogram was assessed in the training and validation cohorts.Results: The radiomics signature was significantly associated with HER2 status in both training(P<0.001) and validation(P=0.023) cohorts. The prediction model that incorporated the radiomics signature and carcinoembryonic antigen(CEA) level demonstrated good discriminative performance for HER2 status prediction,with an area under the curve(AUC) of 0.799 [95% confidence interval(95% CI): 0.704-0.894] in the training cohort and 0.771(95% CI: 0.607-0.934) in the validation cohort. The calibration curve of the radiomics nomogram also showed good calibration. Decision curve analysis showed that the radiomics nomogram was useful.Conclusions: We built and validated a radiomics nomogram with good performance for HER2 status prediction in gastric cancer. This radiomics nomogram could serve as a non-invasive tool to predict HER2 status and guide clinical treatment.

Radiomics-based predictive risk score: A scoring system for preoperatively predicting risk of lymph node metastasis in patients with resectable non-small cell lung cancer

Objective: To develop and validate a radiomics-based predictive risk score(RPRS) for preoperative prediction of lymph node(LN) metastasis in patients with resectable non-small cell lung cancer(NSCLC).Methods: We retrospectively analyzed 717 who underwent surgical resection for primary NSCLC with systematic mediastinal lymphadenectomy from October 2007 to July 2016. By using the method of radiomics analysis, 591 computed tomography(CT)-based radiomics features were extracted, and the radiomics-based classifier was constructed. Then, using multivariable logistic regression analysis, a weighted score RPRS was derived to identify LN metastasis. Apparent prediction performance of RPRS was assessed with its calibration,discrimination, and clinical usefulness.Results: The radiomics-based classifier was constructed, which consisted of 13 selected radiomics features.Multivariate models demonstrated that radiomics-based classifier, age group, tumor diameter, tumor location, and CT-based LN status were independent predictors. When we assigned the corresponding score to each variable,patients with RPRSs of 0-3, 4-5, 6, 7-8, and 9 had distinctly very low(0%-20%), low(21%-40%), intermediate(41%-60%), high(61%-80%), and very high(81%-100%) risks of LN involvement, respectively. The developed RPRS showed good discrimination and satisfactory calibration (C-index: 0.785, 95% confidence interval(95% CI):0.780-0.790)Additionally, RPRS outperformed the clinicopathologic-based characteristics model with net reclassification index(NRI) of 0.711(95% CI: 0.555-0.867).Conclusions: The novel clinical scoring system developed as RPRS can serve as an easy-to-use tool to facilitate the preoperatively individualized prediction of LN metastasis in patients with resectable NSCLC. This stratification of patients according to their LN status may provide a basis for individualized treatment.

Development and validation of a CT-based radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma

Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologically confirmed GA(low-grade:n=154;high-grade:n=438)from January 2008 to March 2018 who were divided into training(n=450)and validation(n=142)sets according to the time of computed tomography(CT)examination.Radiomic features were extracted from the portal venous phase CT images.The Mann-Whitney U test and the least absolute shrinkage and selection operator(LASSO)regression model were used for feature selection,data dimension reduction and radiomics signature construction.Multivariable logistic regression analysis was applied to develop the prediction model.The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram.The performance of the nomogram was assessed with respect to its calibration and discrimination.Results:A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA(P<0.001 for both training and validation sets).A nomogram including the radiomics signature and tumor location as predictors was developed.The model showed both good calibration and good discrimination,in which C-index in the training set,0.752[95%confidence interval(95%CI):0.701-0.803];C-index in the validation set,0.793(95%CI:0.711-0.874).Conclusions:This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures,which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.

Coupling radiomics analysis of CT image with diversification of tumor ecosystem: A new insight to overall survival in stage Ⅰ-Ⅲ colorectal cancer

Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.Methods: We retrospectively identified 161 consecutive patients with stage Ⅰ-Ⅲ CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.Results: The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio(HR)=6.670;95% confidence interval(95% CI): 3.433-12.956;P<0.001), external validation cohort 1(HR=2.866;95% CI: 1.646-4.990;P<0.001) and external validation cohort 2(HR=3.342;95% CI: 1.289-8.663;P=0.002).Incorporating the EcoRad signature into the prediction model presented a higher prediction ability(P<0.001) with respect to the C-index(0.813, 95% CI: 0.804-0.822 in the training cohort;0.758, 95% CI: 0.751-0.765 in the external validation cohort 1;and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis(TNM) system, as well as a better calibration,improved reclassification and superior clinical usefulness.Conclusions: This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage Ⅰ-Ⅲ CRC patients.

Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model

Objective： To develop and validate a radiomics prediction model for individualized prediction of perineural invasion（PNI） in colorectal cancer（CRC）.Methods： After computed tomography（CT） radiomics features extraction, a radiomics signature was constructed in derivation cohort（346 CRC patients）. A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen（CEA） level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation（separate from the cohort used to build the model） was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram.Results： The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell＇s concordance index（c-index）： 0.817; 95% confidence interval（95% CI）： 0.811–0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination（c-index： 0.803; 95% CI： 0.794–0.812）.Conclusions： Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.

New Diterpenoid Alkaloids from Delphinium Souliei Franch

Continuing investigation of Delphinium souliei Franch yielded two minor new diterpenoid alkaloids--souline E(1) and souline F(2), their structures were determined on the basis of spectroscopic evidences.

Diterpenoid Alkaloids from Delphinium Tongolense

The phytochemical investigation of Delphinium tongolense Franch. yielded two new diterpenoid alkaloids tongolenine C and tongolenine D. Their structures were elucidated by spectroscopical methods.

Effect and mechanism of neurotrophin 3 on inhibiting dexamethasone-induced mouse MC3T3-E1 osteoblast apoptosis

Objective:To study the effect and mechanism of neurotrophin 3 (NT-3) on inhibiting dexamethasone (DEX)-induced mouse MC3T3-E1 osteoblast apoptosis.Methods:Mouse MC3T3-E1 osteoblasts were cultured and divided into groups. Control group were treated with DMEM without drugs, DEX group were treated with DMEM containing 5μmol/L dexamethasone, and NT-3 group were treated with DMEM containing 5μmol/L dexamethasone and 100ng/mL NT-3. Apoptosis rate, proliferation viability, osteogenesis marker contents as well as apoptosis gene and PI3K/AKT/mTOR signaling pathway molecule expression were detected.Results: The apoptosis rate as well as bax and caspase-3 expression in the cells of DEX group was significantly higher than those of control group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly lower than those of control group (P<0.05);the apoptosis rate as well as bax and caspase-3 expression in the cells of NT-3 group was significantly lower than those of DEX group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly higher than those of DEX group (P<0.05).Conclusion:NT-3 has inhibiting effect on the dexamethasone-induced mouse MC3T3-E1 osteoblast apoptosis, and the possible mechanism of this effect is to activate the PI3K/AKT/mTOR signaling pathway.

鱼际穴实体解剖结构

目的 探索鱼际穴实体解剖结构。方法 (1)查阅归纳古籍中鱼际穴定位及其演变。(2)25名志愿者鱼际区域分区按压,确定出现“穴感”位置并标记。(3)在标记处用毫针针刺观察有无穴感,并根据产生穴感时针尖所在位置、深度参照断层解剖图谱确定穴体初步判定穴体的三维定位。(4)在10侧新鲜人体上肢标本上,根据体表按压和针刺确定的鱼际穴穴体的位置进行显微解剖,探索穴位实体解剖结构。(5)针刺志愿者鱼际穴出现穴感时,用B超确认针尖所在位置。(6)用超声显像仪在10名志愿者手鱼际部找到鱼际穴穴体位置,在B超引导下针刺该位置与其周围组织,验证其区别。结果 (1)古籍中鱼际穴定位,从鱼际部的散脉中逐渐缩小至“舟角沟”以远的凹陷处。(2)分区按压,恒定出现穴感位置在“舟角沟”远端。(3)针刺“舟角沟”远端时穴感最强烈。(4)显微解剖发现鱼际穴处有拇对掌肌肌支及其伴行血管进入肌肉。(5)针刺鱼际穴出现强烈穴感时,针尖位于拇对掌肌肌门处。(6)B超下证实拇对掌肌肌门是鱼际穴实体解剖结构。结论 鱼际穴主穴穴体位于“舟角沟”远端,为拇对掌肌肌门处,另有多个穴体散在分布于整个鱼际区,其中鱼际中、近部皮肤浅静脉丰富区穴体分布相对密集。

Diagnostic Values of Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptor for Benign and Malignant Hydrothorax

Background： Hydrothorax, as one of the common complications of malignant tumors, still cannot be sensitively detected in clinical practice, thus requiring a sensitive, specific method for diagnosis. The aim of this study was to analyze the correlation between levels of vascular endothelial growth factor （VEGF） and epidermal growth factor receptor （EGFR） in patients with benign and malignant hydrothorax. Methods： The contents of VEGF in the pleural effusion and serum of the patients with malignant pleural effusion （n = 35） and benign pleural effusion （n = 30） were detected by double antibody sandwich enzyme linked immunosorbent assay. The gene copy number level of EGFR in pleural effusion was detected by fluorescence in situ hybridization （FISH）. The points with the highest sensitivity and specificity were selected as the critical values to calculate the diagnostic value of the VEGF in pleural effusion and serum, and EGFR gene copy number in pleural effusion. Results： The contents of VEGF in pleural effusion and serum of patients with malignant hydrothorax were （384.91 ± 120.18）, and （129.62 ±46.35） ng/L, respectively, which were significantly higher than those of the patients with benign hydrothorax （207.97 ± 64.04）, （63.49 ± 24.58） ng/L （P 〈 0.01 ）. The sensitivity and specificity of detecting VEGF in pleural effusion were 80.0% and 96.7% （the boundary value was 297.06 ng/L）, respectively for diagnosing benign and malignant hydrothorax. The sensitivity and specificity of serum were 74.3% and 96.7%, respectively （the boundary value was 99.21 ng/L） for diagnosing benign and malignant hydrothorax. The diagnostic efficiencies of EGFR and VEGF in hydrothorax were similar. There was a significant correlation between EGFR and VEGF in hydrothorax （P 〈 0.01 ）. Conclusions： VEGF and EGFR play important roles in the formation of pleural effusion. VEGF differed significantly in benign and malignant pleural effusions, which contributed to differential diagnosis results of benign and malignant pleural effusions. It is feasible to detect the gene copy number of the pleural effusion cell mass EGFR by FISH technique. Joint detection can improve the diagnostic sensitivity.

NOD-like receptors mediated activation of eosinophils interacting with bronchial epithelial cells： a link between innate immunity and allergic asthma

Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain （NOD）-Iike receptors （NLRs）. We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand 7-D-glutamyl-meso-diaminopimelic acid （iE-DAP） and NOD2 ligand muramyl dipeptide （MDP）. However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule （ICAM）-I on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system （all P〈0.05）. Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-KB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 （Th2） cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice （all P〈0.05）. This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.

Junctional and somatic hypermutation-induced CX4C motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody

Induction of broadly neutralizing monoclonal antibodies(bNAbs)that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus(HCV)vaccine research.The study of bNAbs arising in natural infection is essential in this endeavor.We generated a human antibody,8D6,recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient.This antibody shows broadly neutralizing activity,which covers a pan-genotypic panel of cell culture-derived HCV virions(HCVcc).Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on E2.We describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad neutralization.We found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge(C-C)motif in the CDRH3 is critical for the broad neutralization and binding activity of 8D6.This motif is conserved among a series of broadly neutralizing HCV antibodies,indicating a common binding model.Next,the 8D6 inferred germline(iGL)was reconstructed and tested for its binding affinity and neutralization activity.Interestingly,8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain,suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce bNAbs.Overall,our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3,while its iGL can serve as a probe to identify potential HCV vaccine strains.

B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role of anti-phosphatidylserine (PS) autoantibodies in the development of LN. Elevated serum PS-specific IgG levels were measured in model mice and SLE patients, especially in those with LN. PS-specific IgG accumulation was found in the kidney biopsies of LN patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type that secretes PS-specific IgG in both lupus model mice and patients. Adoptive transfer of PS-specific B1a cells accelerated the PS-specific autoimmune response and renal damage in recipient lupus model mice, whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components, while blockade of TLR signal cascades by DNase I digestion and inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of the TLR/Syk signaling cascade inhibits PS-specific B1-cell expansion provide new insights into lupus pathogenesis and may facilitate the development of novel therapeutic targets for the treatment of LN in SLE.