Fifty whitespotted bamboo sharks (Chiloscyllium playgiosum) of both sexes were used to establish a large capacity variable domain of the new antigen receptor (VNAR) library with a total capacity of over 10⁹ colony-forming units (CFU). It was applied to screen VNARs against human serum albumin (HSA) and human transcription factor EB (TFEB), respectively. Meanwhile, VNAR libraries specific to HSA and TFEB with capacities above 10⁸ CFU were obtained following conventional immunization. These two approaches were systematically studied in terms of VNAR yield and composition. By comparing the VNAR sequences obtained from naïve and antigen-immunized libraries, we found that the complementary-determining region 3 (CDR3) of the former differs in composition from that of the latter. It shares a higher degree of homology with the naïve library. Meanwhile, the binding efficiency assessed by ELISA is also different between the naïve and antigen-immunized libraries. The binding of VNARs from the TFEB-immunized library appeared to surpass that observed with the naïve libraries, whereas the performance of VNARs from the HSA-immunized library indicated that both the immunized and naïve libraries for HSA had positive binding responses in polyclonal and monoclonal ELISA. The results are useful to develop novel diagnostic and therapeutic products based on shark VNARs.

Purpose: We aimed to identify effectiveness-associated indicators and evaluate the optimal tumor reduction rate (TRR) after two cycles of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer. Methods: This retrospective case-control study included patients who underwent at least four cycles of NAC at the Department of Breast Surgery between February 2013 and February 2020. A regression nomogram model for predicting pathological responses was constructed based on potential indicators. Results: A total of 784 patients were included, of whom 170 (21.68%) reported pathological complete response (pCR) after NAC and 614 (78.32%) had residual invasive tumors. The clinical T stage, clinical N stage, molecular subtype, and TRR were identified as independent predictors of pCR. Patients with a TRR > 35% were more likely to achieve pCR (odds ratio, 5.396; 95% confidence interval [CI], 3.299–8.825). The receiver operating characteristic (ROC) curve was plotted using the probability value, and the area under the ROC curve was 0.892 (95% CI, 0.863–0.922). Conclusion TRR > 35% is predictive of pCR after two cycles of NAC, and an early evaluation model using a nomogram based on five indicators, age, clinical T stage, clinical N stage, molecular subtype, and TRR, is applicable in patients with invasive breast cancer.

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

Fucoidan is a kind of sulfated polysaccharide with various biological activities that mainly exists in the cell walls of brown algae. It is also found in marine invertebrates such as sea cucumbers and sea urchins. Fucoidan has received a lot of attention due to its tumor-killing and immune-boosting properties. Moreover, the combination of fucoidan with chemotherapeutic drugs not only improves antitumor efficacy but also reduces the side effects of these drugs. The function of fucoidan is closely correlated with its structure, molecular weight, degree of sulfation, monosaccharide component, algae source, and time of collection. In this review, the antitumor and immunomodulatory effects of fucoidan are reviewed from the aspects of promoting cell apoptosis, inducing cell cycle arrest, inhibiting angiogenesis and cell migration, and activating immune cells, to provide theoretical guidance for the development and clinical application of fucoidan.

Objective:To investigate the regulatory effects of nuclear factor-κB (NF-κB) on dendritic cell (DC) maturation and function through solute carrier family 1 member 2 (Slc1a2).Methods:Mouse bone marrow-derived DCs were transfected with Slc1a2-specific siRNA and an overexpression Slc1a2 eukaryotic expression vector. The real-time fluorescence quantitation (RT-PCR) and Western Blot methods were used to detect knockdown and overexpression efficiency. The expression of surface molecules (CD40, CD80) and major histocompatibility complex Ⅱ (MHCⅡ) of DCs was detected by flow cytometry. ELISA was used to detect the secretion of the cytokines interleukin (IL)-12, IL-6, and transforming growth factor-β (TGF-β). The effects of knockdown of Slc1a2 on DC maturation and function and the effects of overexpression of Slc1a2 on DC maturation and function were reflected by the above assay results. A mixed lymphocyte culture assay was used to investigate the effect of Slc1a2 on T cell proliferation, and an ELISA was used to detect the lavel of IL-17A. Changes in the relative fluorescence intensity of FITC in DCs were analyzed by flow cytometry to investigate the ability of Slc1a2 overexpression on antigen phagocytosis. Finally, DCs were pretreated with an NF-κB inhibitor, toluoylphenylalanine chloromethyl ketone (TPCK), and the effect of TPCK on the expression of Slc1a2 in DCs and DC maturation was examined.Results:Slc1a2 expression was found to be high in DC treated with lipopolysaccharides (LPS) ( P<0.001). The knockdown of Slc1a2 decreased DC maturation and ability to stimulate the proliferation of CD4 + T cells ( P<0.001) and inhibited IL-17 secretion ( P<0.01). Overexpression of Slc1a2 promoted DC maturation and ability to stimulate the proliferation of CD4 + T cells(all P<0.01) Pretreatment of DC with the NF-κB inhibitor TPCK inhibited the expression of Slc1a2 at mRNA and protein levels induced by LPS. Conclusions:NF-κB regulates Slc1a2 expression, which affects the maturation and function of DC.

Objective:To investigate the status quo of professional identity of nursing undergraduates in Beijing and analyze its influencing factors and to provide basis for carrying out professional identity education of nursing undergraduates.Methods:Using the convenient sampling method, a total of 726 nursing undergraduates from four undergraduate colleges in Beijing from June to September 2020 were selected as research objects. General information questionnaire, Professional Identity Questionnaire for Nurse Students (PIQNS) and Professional Self-efficacy Questionnaire for Nurse Students (PSQNS) were used to investigate them. A total of 726 questionnaires were distributed and 615 valid questionnaires were recovered.Results:The total scores of PIQNS and PSQNS among 615 nursing undergraduates in Beijing were respectively 55.00 (36.00, 66.00) and 86.00 (60.00, 101.00) . There was a positive correlation between PIQNS total score and PSQNS total score of nursing undergraduates ( r=0.928, P<0.01) . The results of multiple linear regression analysis showed that gender, whether there was a class tenure, whether he was an only child, reasons for attending nursing major and whether he had clinical practice or internship experience were the influencing factors of professional identity of nursing undergraduates in Beijing ( P<0.01) , which could explain 17.6% of the total variation. Conclusions:The professional identity of nursing undergraduates in Beijing is at the medium level and still needs to be improved. Nursing educators should pay attention to the emotional and psychological status of nursing undergraduates and take appropriate measures to provide vocational education for nursing undergraduates, so as to further improve their professional identity.

Objective The aim of this study was to evaluate whether PRDM16 gene polymorphisms were associated with dyslipidemia. Methods The polymorphisms of rs2651899, rs2236518, rs870171, and rs2282198 in PRDM16 gene in 528 participants were genotyped by the method of snapshot or ligase detection reaction. The genotype differences and the allele differences between the case group and the control group were analyzed. Linkage disequilibrium analysis was performed with SHE-sis online software. The interaction between rs2651899, rs2236518, rs870171, rs2282198 and gender, age, BMI were analyzed by MDR software. Results The frequency of allele A in rs2651899 locus was significantly higher in low HDL-C group compared with that in control group[OR(95%CI)=1.32(1.02-1.71), P=0.033]. The frequency of A/C genotype in rs870171 was significantly different between LDL-C abnormal group and control group[OR(95% CI)=1.97(1.01-3.86), P=0.037]. There may be interaction between rs2236518 and sex, which is a risk factor for low HDL-C[Model Ⅱ: OR(95% CI)=1.958(1.366-2.809), P<0.01]. There may be interactions among rs2651899, rs2236518, rs870171, and rs2282198, which seemed to be risk factors for lower HDL-C[Model Ⅳ: OR(95% CI)=3.991(2.707-5.884), P<0.01]. rs870171, rs2282198 may have interaction with age, which is a risk factor for high LDL-C [Model Ⅶ: OR(95%CI)=3.991(2.707-5.884), P<0.01]. Conclusion Allele A of rs2651899 may be a risk factor to low HDL-C. Under the codominant inheritance patterns, genotype A/C of rs870171 may be a risk factor to high LDL-C. In addition, there may be interaction between SNPs with gender and age.

Objective: To investigate the impact of intensified maintenance therapy on the prognosis of children and adolescents with advanced lymphoblastic lymphoma (LBL) . Methods: Retrospective analysis on the treatment results of children and adolescents with stage Ⅲ and stage Ⅳ LBL who underwent BFM-NHL-90/-95 regimen without prophylactic radiotherapy. The intensified therapy group included the patients admitted from 1998 to 2005, while others were classified as the non-intensified therapy group. Patients in the intensified therapy group were intravenously treated with "etoposide phosphate plus cytrarabine" and high-dose methotrexate alternately per 2.5-3 months in addition to the oral chemotherapy with 6-mercaptopurine and methotrexate during the maintenance phase. Results: A total of 187 LBL patients were enrolled. The rates of 5-year event free survival were (76.9 ± 5.8) % and (77.9 ± 4.3) % (χ²=0.249, P=0.617) respectively, in the intensified therapy (n=52) and the non-intensified therapy groups (n=135) , while the rates of 5-year overall survival of them were (78.8 ± 5.7) % and (79.8±4.1) % (χ²=0.353, P=0.552) , respectively. Stratified by stage, immunological type as well as risk stratification, the rates of long-term survival were similar between the two groups. During the maintenance phase, the rates of grade Ⅲ and Ⅳ myelosuppression in the intensified therapy and the non-intensified maintenance groups were 55.8% and 18.5%, respectively (χ²=25.363, P<0.05) . Conclusion Intensified maintenance therapy failed to improve the prognosis of patients with advanced LBL.

Adult ; Female ; Humans ; Male ; Occupational Exposure ; adverse effects ; Organic Chemicals ; adverse effects ; Paint ; adverse effects ; Solvents ; adverse effects

Objective:To investigate the correlation between anthropometric indices and arteriosclerosis detection indicators in the middle-aged and the elderly .Methods: A cross-sectional descriptive study was made of 1 626 individuals ( diabetics patients 23.37%, hypertensive subjects 39.48% and healthy individuals 37.15%), aged 45 to 90 years [mean age:(61.60 ±10.22) years)] in Shijingshan Dis-trict, Beijing.Their measurements:body mass index (BMI), waist circumference (WC), and waist to height ratio ( WHtR ) .Arterial stiffness was assessed according to brachial-ankle pulse wave velocity (baPWV), intima-media thickness (IMT), augmentation index (AI) and ankle-brachial index (ABI), which were measured by noninvasive detectors and equipment .The correlations between the various indi-cators were analyzed .Results:The percentages of the hypertensive and diabetic groups of central obesity ( male WC>85 cm, female WC >80 cm or WHtR>0.5 ) and of general obesity ( BMI>28 kg/m2 ) were significantly higher than those of the healthy group ( P<0 .01 ) .The difference between the two disease groups was not significant ( P>0 .05 ) .There was a moderate positive correlation between the measures of abdominal obesity (WHtR and WC) and the general obesity indicators (BMI) (r=0.710 and 0.716) .In the healthy group , WC and WHtR showed positive correlation with baPWV , IMT and ABI, and negative correlation with AI 75 .BMI showed positive correlation with IMT and negative correla-tion with AI75 , and no correlation with baPWV and ABI .There was negative correlation between BMI and baPWV in the diabetic group .In the hypertension group , we found negative correlation between BMI and baPWV, maximum IMT, AI75 , and also between WC and AI 75 .The simple regression straight line of baPWV versus the anthropometric parameters showed that the regression equations were y =0 .949 +1.379 x (baPWV vs.WHtR, R2 =0.046, P<0.001) and y=1.133+0.006x (baPWV vs.WC, R2 =0.027, P<0.001), respectively.baPWV and BMI did not have a linear relationship (P =0.62). Conclusion:WHtR and WC are superior to BMI indices in predicting arteriosclerosis .Anthropometric measurements for central obesity are good predictors of cardiovascular risk .