PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis

Abstract Background: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). Methods: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB. Result: When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. Conclusion: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.

Comparison of tooth movement and biological response resulting from different force magnitudes combined with osteoperforation in rabbits

Abstract Objective To compare tooth movement rate and histological responses with three different force magnitude designs under osteoperforation in rabbit models. Methodology 48 rabbits were divided into three groups: Group A, Group B, and Group C, with traction force of 50 g, 100 g, 150 g, respectively. Osteoperforation was performed at the mesial of the right mandibular first premolar, the left side was not affected. One mini-screw was inserted into bones between two central incisors. Coil springs were fixed to the first premolars and the mini-screw. Tooth movement distance was calculated, and immunohistochemical staining of PCNA, OCN, VEGF, and TGF-β1 was analyzed. Results The tooth movement distance on the surgical side was larger than the control side in all groups (P<0.01). No significant intergroup difference was observed for the surgical side in tooth movement distance among the three groups (P>0.05). For the control side, tooth movement distance in Group A was significantly smaller than Groups B and C (P<0.001); no significant difference in tooth movement distance between Group B and Group C was observed (P>0.05). On the tension area of the moving premolar, labeling of PCNA, OCN, VEGF and TGF-β1 were confirmed in alveolar bone and periodontal ligament in all groups. PCNA, OCN, VEGF and TGF-β1 on the surgical side was larger than the control side in all groups (P<0.001). Conclusion Osteoperforation could accelerate orthodontic tooth movement rate in rabbits. Fast osteoperforation-assisted tooth movement in rabbits was achieve with light 50 g traction.

Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study / 부인종양

OBJECTIVE: To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS: Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS: There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07–0.68; p=0.010). Women in their 40s–50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03–1.49; p=0.020). CONCLUSION: In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.

Magnetic nanoparticle method for detecting circulating tumor cells of lung cancer: A pilot study / 中国胸心血管外科临床杂志

@#Objective    To explore the diagnostic value of circulating tumor cells (CTC) measured by magnetic nanoparticle method in lung cancer. Methods    (1) We measured binding capability of A549 or NCI-H1965 cell lines with recognition peptide and capture efficiency by adding tumor cells into the whole blood of healthy human. (2) We measured CTC of 34 patients suspected with lung cancer, and the counting results of CTC were compared with the following pathological results. Results    (1) The binding capability was 80.0%±6.0% for A549 and 70.1%±4.8% for H1957, while the capture efficiency was 57.3%±7.0% for A549 and 37.3%±6.1% for H1975. (2) CTCs were identified in 71.9% of patients with lung cancer. The specificity was 83.3%, and area under receiver operating characteristic (ROC) curve was 0.792 (P=0.003). Conclusion    CTC measured by magnetic nanoparticle method has promising application in the diagnosis of lung cancer.

Outcomes and prognostic factors of surgically treated thymic carcinoma / 中国胸心血管外科临床杂志

@#Objective     To evaluate the influence of resection status, pathological type, pathological stage and postoperative adjuvant therapy on prognosis of surgically treated thymic carcinoma. Methods     In this retrospective study, 56 patients with surgically treated thymic carcinoma in the Department of Thoracic Surgery, Peking Union Medical College Hospital from January 2005 to December 2015 were enrolled. There were 30 males and 26 females aged 52.1±11.5 years ranging from 22 to 81 years. The survival curve was performed by Kaplan-Meier method. The prognostic factors affecting overall survival (OS) and disease-free survival (DFS) were analyzed by one-way analysis of variance (ANOVA). Results     R0 resection was performed in 37 patients (67.9%), and other resections in 19 (32.1%); 13 patients suffered thymic carcinoma with Masaoka stage Ⅰ-Ⅱ, 26 Ⅲ, and 17 Ⅳ. Low-grade thymic carcinoma was found in 42 patients, and high-grade in 14. Postoperative radiotherapy, chemotherapy and chemoradiotherapy were performed on 17, 12 and 18 patients respectively and 9 patients were untreated. Forty-one patients was followed up for 1 to 10 years, and the follow-up rate was 73%. The 1-, 3- and 5-year OS rates were 93%, 74% and 61%, respectively. Resection status and pathological stage affected OS. Postoperative radiotherapy after R0 resection affected DFS, but did not affect OS. Conclusion     Most patients with thymic carcinoma after surgery can survive for a long period, and R0 resection is the most important prognostic factor of thymic carcinoma. Postoperative radiotherapy after R0 resection in patients with Masaoka stage Ⅱ-Ⅲ is recommended.

Value of polypeptide-based nanomagnetic circulating tumor cells detection for the differential diagnosis of pulmonary nodules / 中国胸心血管外科临床杂志

@#Objective    To explore the efficacy of a novel detection technique of circulating tumor cells (CTCs) to identify benign and malignant lung nodules. Methods     Nanomagnetic CTC detection based on polypeptide with epithelial cell adhesion molecule (EpCAM)-specific recognition was performed on enrolled patients with pulmonary nodules. There were 73 patients including 48 patients with malignant lesions as a malignant group and 25 patients with benign lesion as a benign group. There were 13 males and 35 females at age of 57.0±11.9 years in the malignant group and 11 males and 14 females at age of 53.1±13.2 years in the benign group. e calculated the differential diagnostic efficacy of CTC count, and conducted subgroup analysis according to the consolidation-tumor ratio, while compared with PET/CT on the efficacy. Results     CTC count of the malignant group was significantly higher than that of the benign group  (0.50/ml vs. 0.00/ml, P<0.05). Subgroup analysis according to consolidation tumor ratio (CTR) revealed that the difference was statistically significant in pure ground glass (pGGO) nodules 1.00/ml vs. 0.00/ml, P<0.05), but not in part-solid or pure solid nodules. For pGGO nodules, the area under the receiver operating characteristic (ROC) curve of CTC count was 0.833, which was significantly higher than that of maximum of standardized uptake value (SUVmax) (P<0.001). Its sensitivity and specificity was 80.0% and 83.3%, respectively. Conclusion     The peptide-based nanomagnetic CTC detection system can differentiate malignant tumor and benign lesions in pulmonary nodules presented as pGGO. It is of great clinical potential as a noninvasive, nonradiating method to identify malignancies in pulmonary nodules.

Traumatismos causados por el tránsito en países en desarrollo: agenda de investigación y de acción / Road traffic injuries in developing countries: research and action agenda

Los traumatismos causados por el tránsito son la principal causa de muerte en personas de 10-24 años a nivel mundial y representan alrededor del 15% de todas las muertes en varones. La carga de enfermedad de los traumatismos causados por el tránsito está distribuida de manera desigual entre los países pues la tasa de mortalidad más alta es ochenta veces superior a las más baja. Existe una clara desigualdad en el riesgo de ocurrencia de traumatismos causados por el tránsito, siendo notoriamente mayor en los países en desarrollo. Esta desigualdad se constituye como un reto mundial importante y se debe, aunque no sean los únicos factores, a muchas razones, incluyendo la rápida motorización y la pobre infraestructura. Este artículo hace énfasis en varios aspectos fundamentales cuya finalidad es informar a los programas diseñados para prevenir los traumatismos causados por el tránsito en los países en desarrollo, donde esta situación está más extendida. En primer lugar, la seguridad vial es un tema de desarrollo; en segundo lugar, los traumatismos causados por el tránsito constituyen un problema importante para la salud; en tercer lugar, los traumatismos causados por el tránsito pueden ser prevenidos mediante la implementación de medidas científicas adecuadas; en cuarto lugar, es necesaria la atención de emergencias hospitalarias y prehospitalarias; y, finalmente, la investigación en los traumatismos causados por el tránsito está relegada en los países de ingresos bajos y medios. Se discute además la repercusión de estos avances para el Perú.

Road traffic injury (RTI) is the leading cause of death in persons aged 10-24 worldwide and accounts for about 15 per cent of all male deaths. The burden of RTI is unevenly distributed amongst countries with over eighty-fold differences between the highest and lowest death rates. Thus the unequal risk of RTI occurring in the developing world, due to many reasons, including but not limited to rapid motorization and poor infrastructure, is a major global challenge. This editorial highlights a number of key issues that must inform programs designed to prevent RTI in the developing world, where the epidemicis all the more insidious. Firstly, road safety is a development issue; secondly, road traffic injury is a major health issue; thirdly, road traffic injuries can be prevented by the implementation of scientific measures; fourthly, pre-hospital and hospital emergency care is needed; and fifthly, research on RTI is neglected in low-income and middle-income countries. The repercussion of such progress to Peru is also discussed.