To develop a method for determining the antibody-dependent cell-mediated phagocytosis (ADCP) activity of human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) based on the reporter gene assay, we established an ADCP activity assay with Jurkat/NFAT/FcγRIIa cells as the effector cells and BT474 as the target cells. Then, the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were optimized by the method of design of experiment (DOE). The method showed a significant dose-response relationship, which was complied with the four-parameter equation: y=(A-D)/[1+(x/C)^B]+D. The durability ranges of the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were (2.5-4.0)×10⁵ cells/mL, 3-5, 1.0-2.0 h, 0 h, and 5.0-6.0 h, respectively. The results of the methodological validation showed that the linear equation was y=1.106 8x-0.011 6, r=0.969 2. The established method showed the relative accuracy ranging from -6.59% to 2.98% and the geometric coefficient of variation less than 11% in the intermediate precision test. Furthermore, the method was target-specific. The method was then applied to the determination of ADCP activity of HER2-targeted ADC, demonstrating the result of (103.5±5.7)%. We developed a reporter gene assay for determining the ADCP activity of HER2-targeted ADC and the assay demonstrated high accuracy and good reproducibility, which proposes a highly efficient and approache for evaluating ADCP effect of this HER2-targeted ADC, and also provides a referable technique for characterizing the Fc effector functions of ADCs with diverse targets.
Humans ; Receptor, ErbB-2/immunology* ; Phagocytosis/drug effects* ; Immunoconjugates/immunology* ; Genes, Reporter ; Antibody-Dependent Cell Cytotoxicity ; Jurkat Cells

Objective: To explore the hemorrhagic transformation(HT) and its effect on prognosis in patients with acute ischemic stroke(AIS) after mechanical thrombectomy(MT). Methods: A total of 114 patients with AIS received MT were enrolled. The modified Rankin Scale was used to evaluate the clinical outcome at 90 days of onset(0-2 points were good prognosis; 3-6 points were poor prognosis). The patients were divided into HT group(n=25) and non-HT group(n=89) according to their HT conditions. Binomial Logistic regression analysis was performed to determine the vascular risk factors of HT after MT and the effect of HT on prognosis. Results: Among 114 patients, there were 25 cases of HT and 89 cases of non HT. The proportion of patients with diabetes in HT group was significantly higher than that in non-HT group. The NIHSS score of HT group at discharge was significantly higher than that in non-HT group. The proportion with good prognosis at 90 days in HT group was significantly lower than that in non-HT group(allP<0.05). Binomial Logistic regression analysis showed that diabetes, high levels of cholesterol and smoking were the major vascular risk factors for HT after thrombectomy(allP<0.05). HT was an important factor affecting the poor prognosis after arterial thrombectomy(P=0.026). Conclusion Diabetes, high levels of cholesterol and smoking are the main risk factors of HT after MT for AIS. HT is an independent risk factor for poor prognosis after MT.

Objective To study the effect of noise pollution on serum hormone and heat shock protein-70(Hsp-70)levels in rats. Methods Forty male Wistar rats were randomly divided into control group(normal), experimental group(further divided into 35,65 and 85 dB three groups), each group 10 animals, stimulated for 30 min once a day, continually stimulated for consecutive 20 days. On the 21st day of experiment,the serum noradrenaline(NA),testosterone (T),dopamine(DA)and Hsp-70 levels were determined by enzyme-linked immunosorbent assay(ELISA). Results Compared with the control group, the body weight of experimental group(35, 65 and 85 dB groups)was reduced by 23.45%,30.13%, and 35.64%, respectively The serum T and DA levels were decreased by 9.12%, 20.06%, 37.99% and 15.49%, 8.31%, 24.88%, respectively; while the serum NA and Hsp-70 levels were increased by 35.08%, 171.52%,197.86%, and 39.34%, 195.09%, and 285.25%, respectively. All the result showed a significant difference(P<0.01). Conclusions Noise pollution can significantly affect the serum levels of hormone and heat shock protein-70 expression in rats.

Lipopolysaccharide(LPS),lipteichoic acid(LTA) and zymosan can be recognized by Toll-like receptors (TLRs) ex-pressing in the inflammatory cells membrane,such as macrophages,monocytes and endothelial cells,and then induce the secretion of pyrogenic cytokines followed by triggering inflammatory reaction. The signaling pathway mechanisms were summarized, including the extracellular signaling cascades from pyrogens to individual TLRs,and intracellular signaling cascades from TLRs to nucleus.

Based on heat-sensitive moxibustion (HSM) theory, a widely applicable scale was developed to reflect the (arrival of ) sensation of HSM. By documentary method and interviewing method, the items of describing sensation of HSM were collected to establish the pool of candidate items. With expert questionnaire, patient questionnaire and core expert discussion, the items were screened and quantified by method of subjective evaluation to develop the initial draft of the scale. A total of 121 patients were pre-surveyed with the initial draft, and the structural validity of the scale was examined by exploratory factor analysis (principal component) and its internal consistency was assessed by Cronbach's coefficient. As a result, the items in the scale was reduced from 36 to 9; 110 effective questionnaires were reclaimed for statistical analysis. Finally, the scale (Version 1.0) contained 9 items and 4 dimensions, of which, 3 items highlighted the comfort emotional experience, 3 items highlighted autonomic response, 2 items highlighted heat sensation, and 1 item highlighted non-heat sensation. In conclusion, the sensation scale of HSM containes 9 items, which has fair content and structure validity. It is in line with the current clinical understanding of sensation of HSM and has strong clinical operability and wide adaptability.
Hot Temperature ; Humans ; Moxibustion ; Sensation ; Surveys and Questionnaires ; Thermosensing

Objective To study the effect of maca extract on sport fatigue and its antioxidant effect.Methods 50 healthy male Wistar rats were randomly divided into control group (normal breeding,without swimming,equal amount of distilled water for gavage),simple swimming group (swimming,equal amount of distilled water for gavage),swimming and medicine group (divided into maca extract 4.0,8.0 and 16.0 g/(kg· bw) groups,respectively),10 rats in each group.All rats were freely swimming in the circulating water flow daily for 15 days.On the 16th day of experiment,liver tissue samples were collected.The liver lipid peroxide (LPO),superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) and liver glycogen level were determined.Results When rats were administered with maca extract at the doses of 4.0,8.0,16.0 g/(kg· bw),respectively,the swimming time before sinking and the total swimming time were increased by 18.99%,64.46% and 90.69%,and 18.99%,56.23% and 94.72%,respectively,while the numbers of times of sinking were decreased by 27.44%,42.86%,64.11% (P<0.01),respectively,compared with the swimming rats without maca extract treatment.The LPO content in the liver of rats treated with maca extract 4.0,8.0,16.0 g/(kg· bw) were reduced by 31.31%,42.00% and 31.31%,respectively,while the levels of SOD,GSH-Px and liver glycogen were enhanced by 25.92%,31.82%,62.09%,12.33%,23.01%,46.36% and 17.83%,44.69%,62.99%,respectively,over those of rats without maca extract treatment.Conclusions Maca extract reduces the liver LPO level,increases liver glycogen level,improves the SOD and GSH-Px activity,therefore,plays a protective role in sport fatigue.

OBJECTIVETo observe the clinical efficacy differences among long-snake moxibustion, warm needling and western medication on rheumatoid arthritis and explore its effect mechanism.

METHODSOne hundred and twenty patients were randomized into a long-snake moxibustion group, a warm needling group and a western medication group, 40 cases in each one. In the long-snake moxibustion group, the long-snake moxibustion was used. The ginger-isolated moxibustion was applied along the governor vessel, from Dazhui (GV 14) to Yaoshu (GV 2), once a month, for 2 months. In the warm needling group, the main points included Dazhui (GV 14), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Zhiyang (GV 9), Mingmen (GV 4) and Yaoyangguan (GV 3). The warm needling technique was used at 4 to 5 points each time, and 3 moxa cones were required at each points. The treatment was given once every two days, for 2 months. In the western medication group, methotrexate was prescribed for oral administration, 10 mg each time, once a week. If the joint pain score or joint swelling score was up to 6, diclofenac sodium was combined, 25 mg each time, 3 times a day, for 2 months. The symptom score, physical sign score, the visual analogue scale (VAS) score, levels of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), immunoglobulin M (IgM) and immunoglobulin G (IgG) were observed before and after treatment in the patients of the three groups.

RESULTSThe treatments relieved the symptoms and physical signs of rheumatoid arthritis and improved VAS score and the levels of serum RF, ESR, CRP, IgM and IgG in all of the three groups (all<0.01). The efficacy in the long-snake moxibustion group was significantly better than that in the warm needling group and the western medication group (<0.05,<0.01).

CONCLUSIONSThe long-snake moxibustion achieves the significant clinical efficacy on rheumatoid arthritis, better than warm needling therapy and methotrexate. This therapy much better reduces immune response and alleviates the sickness.

Objective: To compare moxibustion sensation and infrared thermography by the assessment of heat-sensitization on Guanyuan (CV 4) in patients with primary dysmenorrhea, and to prove the possibility of adopting infrared thermography as an objective demonstration of acupoints heat-sensitization. Methods: Seventy-one patients with primary dysmenorrhea were enrolled to receive moxibustion and infrared to detect the heat-sensitization of Guanyuan (CV 4). The results were then analyzed and compared. Results: The infrared radiation showed a lower temperature when the acupoint Guanyuan (CV 4) was sensitized in patients with primary dysmenorrhea. Compared with moxibustion sensation, its sensitivity rate (real positive rate) was 76.6%, divergence rate (real negative rate) was 70.1%, and the accuracy rate was 74.6%. After giving moxibustion to Guanyuan (CV 4), the infrared radiation area was significantly expanded longitudinally and transversely. Compared with moxibustion test, the sensitivity rate (real positive rate) of infrared test was 78.7%, divergence rate (real negative rate) was 83.3%, and the accuracy rate was 80.3%. Conclusion: To a certain extent, the heat-sensitization of the acupoint Guanyuan (CV 4) in patients with primary dysmenorrhea can be revealed by infrared thermography. The acupoint heat-sensitization phenomena (heat extension or transmission) after giving moxibustion to the heat-sensitized acupoints can also be demonstratedobjectively by infrared thermography, besides experienced subjectively by the receivers.

Objective: To elucidate the key effects of moxibustion points and quantity of moxibustion used in order to enhance the curative effect of moxibustion therapy. Methods: It analyzed the occurrence rules of acupoint heat-sensitization and its relationship to the moxibustion location and dose, in view of the original definition of acupoints in Nei Jing (Internal Canon) and the acupoint heat-sensitization in clinical practice. Results: (1) The original definition of acupoint is the reflecting area of a disease on surface of the body, which is individualized, motive and sensitive; (2)The location in which heat-sensitization is generated relating to a heat-sensitive acupoint, which therefore depicts the best choice for point selection and also the most accurate area to give moxibustion; (3) The heat-sensitization time can be taken as a clinical index to quantify the moxibustion dose, in order to apply sufficient moxibustion for each individual. Conclusion: The key points for enhancing the curative effect of moxibustion therapy are to identify heat-sensitive points and a scientific moxibustion dose.

Academia-industry collaboration is defined as the cooperation between both sides,utilizing the capitals and pathways of the industrial side as well as the faculties and facilities of the academic side to push the products to the market with cost minimization as well as profit or utility maximization.All the group members share the results to attain the double win.The six key steps to establish this collaboration include creating the cooperation platform,signing related agreements,constructing related hard and software,setting a company for operation,performing experiment,licensing,patent or technique transfer,products marketing as well as sharing profits.Several issues should be known while this collaboration established in the biomedical field,especially about the ethics of human studies.The influencing factors of its effectiveness would be analyzed in the present paper.