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.

Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

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.

Nighteen people at a restaurant experienced dizziness headaches and other discomforts in six days. According to the description method, the time and location distribution were found to be concentrated. A second Investigation was conducted at the same time as the onset of the case, the test found that the carbon monoxide concentration of second floor up to 539 mg/m 3. The on-site testing found that when 2 steam generator in snack room on the first floor turned on, the carbon monoxide concentration on the top of elevator on the second floor was 1225.0 mg/m 3. After the accident, the restaurant replaced a steam generator, the carbon monoxide concentration on the top of the new and old steam generator were 350 mg/m 3 and >1 000 mg/m 3, respectively. After the steam generators were fitted with exhaust smoke pipe and exhasust hood, the carbon monoxide concentrations of on the top of the vegetable transfer elevator and the room on the second floor were both 0.4 mg/m 3, and there were no cases of recurrence. It was determined that this was a carbon monoxide poisoning incident caused by a high concentration of carbon monoxide emitted by the steam generators, which spread to the second floor of the private room through the vegetable transfer elevator.

Objective:To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen.Methods:The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy.Results:A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021.Conclusions:Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.

Nighteen people at a restaurant experienced dizziness headaches and other discomforts in six days. According to the description method, the time and location distribution were found to be concentrated. A second Investigation was conducted at the same time as the onset of the case, the test found that the carbon monoxide concentration of second floor up to 539 mg/m 3. The on-site testing found that when 2 steam generator in snack room on the first floor turned on, the carbon monoxide concentration on the top of elevator on the second floor was 1225.0 mg/m 3. After the accident, the restaurant replaced a steam generator, the carbon monoxide concentration on the top of the new and old steam generator were 350 mg/m 3 and >1 000 mg/m 3, respectively. After the steam generators were fitted with exhaust smoke pipe and exhasust hood, the carbon monoxide concentrations of on the top of the vegetable transfer elevator and the room on the second floor were both 0.4 mg/m 3, and there were no cases of recurrence. It was determined that this was a carbon monoxide poisoning incident caused by a high concentration of carbon monoxide emitted by the steam generators, which spread to the second floor of the private room through the vegetable transfer elevator.

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 evaluate the feasibility of speckle-tracking echocardiography in detecting left atrial (LA) function impairment in early hypertensive (HT) patients.Methods Echocardiography was performed in 154 HT patients with LA volume index ＜28 ml/m2 and 64 age/gender-matched control subjects.LA global longitudinal strain in late diastole (Sa),systole (Ss),and total strain (Stot =Sa + Ss),strain rate in late diastole (SRa),systole (SRs),and early diastole (SRe) were measured using off-line speckle-tracking analyzing software in apical 4 chamber view.Results Both parameters reflecting LA reservoir function [Stot (23.7 ± 6.0) ％ vs (25.7 ± 5.9) ％,p =0.03 and SRs ( 1.2 ± 0.3) s- 1 vs ( 1.3 ±0.3) s-1,P =0.03]and conduit function [Ss (12.0 ± 5.1)％ vs (14.0±5.7)％,P =0.02 and SRe (1.0 ± 0.4)s- 1 vs ( 1.2 ± 0.4)s- 1,p ＜0.001 ]decreased significantly in HT group than control,while LA pump function parameters (Sa and SRa) had no differences.Ss,Stot and SRe correlated significantly with HT and HT duration.Conclusions LA phasic function are impaired in HT patients with normal LA size.Speckle tracking echocardiography is a promising tool for the early detection of LA dysfunction.