ABSTRACT
The structure of N-glycans on specific proteins can regulate innate and adaptive immunity via sensing environmental signals. Meanwhile, the structural diversity of N-glycans poses analytical challenges that limit the exploration of specific glycosylation functions. In this work, we used THP-1-derived macrophages as examples to show the vast potential of a N-glycan structural interpretation tool StrucGP in N-glycoproteomic analysis. The intact glycopeptides of macrophages were enriched and analyzed using mass spectrometry (MS)-based glycoproteomic approaches, followed by the large-scale mapping of site-specific glycan structures via StrucGP. Results revealed that bisected GlcNAc, core fucosylated, and sialylated glycans (e.g., HexNAc4Hex5Fuc1Neu5Ac1, N4H5F1S1) were increased in M1 and M2 macrophages, especially in the latter. The findings indicated that these structures may be closely related to macrophage polarization. In addition, a high level of glycosylated PD-L1 was observed in M1 macrophages, and the LacNAc moiety was detected at Asn-192 and Asn-200 of PD-L1, and Asn-200 contained Lewis epitopes. The precision structural interpretation of site-specific glycans and subsequent intervention of target glycoproteins and related glycosyltransferases are of great value for the development of new diagnostic and therapeutic approaches for different diseases.
Subject(s)
Humans , B7-H1 Antigen , Glycosylation , Polysaccharides/metabolismABSTRACT
Macrophages are widely distributed immune cells that contribute to tissue homeostasis. Human THP-1 cells have been widely used in various macrophage-associated studies, especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes. However, the molecular characterization of four M2 subtypes (M2a, M2b, M2c, and M2d) derived from THP-1 has not been fully investigated. In this study, we systematically analyzed the protein expression profiles of human THP-1-derived macrophages (M0, M1, M2a, M2b, M2c, and M2d) using quantitative proteomics approaches. The commonly and specially regulated proteins of the four M2 subtypes and their potential biological functions were further investigated. The results showed that M2a and M2b, and M2c and M2d have very similar protein expression profiles. These data could serve as an important resource for studies of macrophages using THP-1 cells, and provide a reference to distinguish different M2 subtypes in macrophage-associated diseases for subsequent clinical research.
Subject(s)
Humans , Macrophages/metabolism , Phenotype , Proteomics , THP-1 CellsABSTRACT
Objective To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with severe dysmenorrhea in a prospective cohort study. Methods From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients′parameters were recorded prospectively, including symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, carrying status of LNG-IUS, menstruation patterns and adverse effects. Changes of scores and patterns of pain during follow-up were analyzed. Results Totally 1 100 women meets inclusion criteria, among which 640 cases (58.18%, 640/1 100) had severe dysmeorrhea, with median follow-up period of 35 months (range 1-60 months), and accumulative carrying rate of 65% at 60 months follow-up. After placement of LNG-IUS, scores of pain and ratio of severe dysmenorrhea had decreased significantly compared with baselines (all P0.05). Conclusion LNG-IUS is effective for adenomyosis of severe dysmenorrhea. Improvement of pain is independent on patients characters, menstruation patterns or adverse effects.
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Objective To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with menorrhea in a prospective study. Methods From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients′parameters were recorded prospectively, including scores of menstruation blood loss, carrying status of IUS, symptoms and scores of dysmenorrhea, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Changes of pictorial chart scores of menstruation and distribution of anemia during follow-up were analyzed. Results Totally 1 100 women meets inclusion criteria, among which 618 cases (56.18%, 618/1 100) had severe menorrhea, with median follow-up period of 28 months (range 1-60 months), and accumulative carrying rate of 66% at 60 months follow-up. After placement of LNG-IUS, compared with baselines, pictorial chart scores and ratio of menorrhea had decreased significantly (all P0.05). Conclusions LNG-IUS is effective for adenomyosis of menorrhea. Improvement of menstruation blood loss is independent on patients characters, menstruation patterns or adverse effects.
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Objective To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system (LNG-IUS) for symptomatic adenomyosis in a prospective cohort study. Methods From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients′ parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results Totally 1 100 cases met inclusion criteria, with median age 36 years (range 20-44 years), median follow-up 35 months (range 1-108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383) and 29.6%(82/277) patients achieved amenorrhea respectively (P12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status (all P>0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of menstruation patterns or adverse effects neither have any risk factor nor have impact on treatment effects.
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Objective To observe the ultrasonographic features of primary squamous cell carcinoma of the breast and its clinical and histopathological characteristics. Methods The ultrasonographic features, clinical and histopathological characteristics of 7 middle-aged women (median age 61 years old) with primary squamous cell carcinoma of the breast confirmed histopathologically from January 1995 to December 2014 in Peking Union Medical College Hospital were retrospectively reviewed. Results There were 8 lesions in seven cases. Six cases were single lesion and 1 case with multiple lesions, the diameters of the lesions were 7.0-60.0 mm [mean (34.0±19.6) mm]. On grayscale ultrasound, 6 lesions with solid compoments were hypoechoic, 2 lesions with solid and cystic compoments were complex echogenic, the lesions all had irregular shape and indistinct margin, 2 lesions had calcifications. On color Doppler flow imaging, 7 lesions had rich blood flow signals (Ⅱor Ⅲ) and 1 lesion had no blood flow signal. On gross histopathological examination, 6 masses were solid, pale-white colored, medium texture and the boundary was not clear. Two masses had cystic cavity. One old patient who was 70 years old had several times chest wall recurrence after mastectomy. On ultrasonography, the lesion showed an anechoic cyst with thick wall. Two chest wall recurrence lesions were cystic with thick wall. Microscopic examination showed squamous cell carcinoma infiltrating into the fiber adipose and skeletal muscle tissue. Conclusions Primary squamous cell carcinoma of the breast is more common in large tumor size. Ultrasound can show the more cysticcomponents of the tumor and abundant vascularity, which is helpful for diagnosis.
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Objective To describe the sonographic features of abdominal wall endometriosis(AWE).Methods 105 consecutive women with proven pathological endometriosis of the abdominal wall were retrospectively recruited.The clinical data and the result of the sonographic examinations were reviewed and described.The AWE lesions were divided into ＜3 cm and ≥3 cm groups according to their maximum diameter.Results The sonographic feature of AWE includes irregular hypoechoic nodules with ill-defined margins,anechoic and hyperechoic ring maybe exist.In color Doppler,most of them showed few internal vascularity.Compared with≥3 cm group,＜3 cm group nodules manifested as shorter latent period,with more superficial location,round or oval shape,peripheral hyperechoic ring and none or few vascularity were more common.As for ≥3 cm group nodules manifested as longer latent period,with deeper location,irregular shape,abundant of vascularity were more common.Conclusions Specific diagnosis of AWE can be made by using high frequency sonography combined with clinical features.More accurate information can be provided by judging the size,range and infiltrative depth.
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Objective To measure total hemoglobin concentration (THC) of breast lesion using US-guided diffused optical tomography(DOT) and to investigate the THC optimal threshold value in different size breast lesions.Methods DOT was performed on 500 breast lesions and surgical pathology was as the gold standard.The optimal diagnostic threshold and the efficacy were figured out.Results There were 265 benign and 235 malignant lesions.In malignant lesions,THC of ≥2 cm lesion group was higher than that of ＜2 cm lesion group(P =0.000).In benign lesions,there was no statistical difference between ≥2 cm group and ＜2 cm group (P =0.13).As for ＜2 cm breast lesions,when a THC threshold value of 146.9 μmol/L and 102.2 μmol/L were used,the sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 74.2％,70.0％,71.7％,62.9％,79.9％ and 86.7％,44.4％,61.6％,51.6％,83％,respectively.As for ≥2 cm breast lesions,when a THC threshold value of 210.4 μmol/L were used,the sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 74.0％,86.7％,79.1％,89.2％,69.2％.Conclusions THC of breast cancer increased with the increasing size of lesions.The different diagnostic threshold value should be used according to different size lesions so as to enhance sensitivity,specificity and accuracy.
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Objective To evaluate the inter-observer variability of static breast sonogram final assessment among observers with different breast imaging experience, using the first edition of the Breast Imaging Reporting and Data System(BI-RADS) for ultrasound. Methods Thirty patients with 30 breast lesions were included who underwent beast lesions resection operation. A pathological diagnosis was available for all 30 lesions:16 (53%) malignant and 14 (47%) benign. Twelve radiologists independently reviewed two sonograms of each lesion, and assigned a final BI-RADS assessment category. Inter-observer variability was measured using kappa statistic. Positive predictive value(PPV) and negative predictive value (NPV) for final assessment were also calculated. Results As for the experienced observers,kappa values of categories 3,4 and 5 were 0.72,0.28 and 0.60,NPV of category 3 was 93% ,PPV of category 5 was 97% ,all of which decreased as the breast imaging experience reduced. PPVs of categories 4a,4b and 4c were 56 % ,88% and 69%, respectively. Conclusions Using BI-RADS final assessment, radiologists with sufficient breast imaging experience can provide accurate and consistent assessment for breast ultrasonography,but the agreement of diagnosis decreased as the breast imaging experience reduced. The clinical feasibility of 4a,4b and 4c subcategories is uncertain.