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 changing trend in the disease burden of gout in China from 1990 to 2021, and analyze the incidence, prevalence, and disability-adjusted life years (DALYs) by age and gender, with comparisons to global patterns, and to predict the disease burden of gout in China in 2030. Methods Data from the Global Burden of Disease (GBD) database were used to analyze changes in gout burden. Joinpoint regression was used to estimate the average annual percentage change (AAPC) with 95% confidence intervals (CIs). Comparative analyses were conducted on data from China and the world, and an ARIMA model was used to project China's gout burden in 2030. Results From 1990 to 2021, China's age-standardized incidence rate (ASIR) rose from 122.52 to 151.61/100,000, exceeding the global rise from 93.09 to 109.07/100,000. The age-standardized prevalence rate (ASPR) in China increased from 640.67/100,000 to 810.35/100,000, compared to a global rise from 536.54/100,000 to 653.81/100,000. The age-standardized DALYs rate (ASDR) in China increased from 20.2/100,000 to 25.43/100,000, surpassing the global increase from 16.67/100,000 to 20.21/100,000. AAPCs for ASIR, ASPR, and ASDR in China were 0.70%, 0.77%, and 0.75%, respectively, all higher than global rates. Middle-aged and elderly men faced the highest burden. It was predicted that there will be a decline in China's ASIR and ASPR by 2030, while ASDR will remain stable. Conclusion The disease burden of gout in China has increased significantly, outpacing global trends. Targeted interventions for hyperuricemia, particularly in elderly men, are crucial to reduce the future disease burden.

Objective To establish a prediction model for futile recanalization after mechanical thrombectomy(MT)in acute anterior circulation large vessel occlusion(ACLVO)stroke patients based on multimodal imaging features,and to evaluate its predictive performance.Methods Retrospectively enrolled consecutive ACLVO patients who underwent MT with successful recanalization(modified thrombolysis in cerebral infarction[mTICI]grade≥2b)at the Department of Neurology of Fuyang People's Hospital between June 2023 and December 2024.Demographic and clinical data were collected,including age,gender,hypertension,diabetes mellitus,atrial fibrillation,smoking history,alcohol consumption history,National Institutes of Health stroke scale(NIHSS)score upon admission,intravenous thrombolysis,wake-up stroke,onset-to-puncture time(OPT),puncture-to-recanalization time(PRT),occlusion vessel(internal carotid artery,middle cerebral artery),treatment method(suction thrombectomy,stent thrombectomy,suction+stent thrombectomy).All patients underwent pre-procedural CT perfusion(CTP)+CT angiography(CTA)of the head and neck.Imaging parameters included hypoperfusion(defined as time to peak＞6 s)volume(HPV),core infarct(defined as cerebral blood flow＜30%)volume(CIV),mismatch ratio(MMR;HPV/CIV),and Tan collateral score(poor collaterals:0-1 score,good collaterals:2-3 score).Patients were followed up at 90 days post-procedure via outpatient clinic or re-admission.Patients with a modified Rankin scale(mRS)score≤2 were classified into the effective recanalization group,while those with mRS score≥3 were classified into the futile recanalization group.Imaging variables with statistically significant differences between the futile recanalization and effective recanalization groups were included in multivariate Logistic regression analysis to identify independent predictors of futile recanalization and construct a nomogram model.The predictive value of the model was assessed using the receiver operating characteristic(ROC)curve.Model calibration was evaluated using the Hosmer-Lemeshow test(goodness-of-fit defined as P＞0.50).Results(1)A total of 105 ACLVO patients with successful MT recanalization were included(65 males,40 females,mean age[66±11]years,ranged 31～87 years).There were 60 patients in the effective recanalization group and 45 in the futile recanalization group.Compared to the effective recanalization group,the futile recanalization group had significantly higher age([69±11]years vs.[63±11]years,P=0.012),higher proportion of diabetes mellitus(33.33%[15/45]vs.16.67%[10/60],P=0.047),higher pre-treatment NIHSS score([15.51±2.73]vs.[13.25±2.71],P＜0.01),longer OPT([516.40±192.48]min vs.[322.98±171.22]min,P＜0.01)and PRT([94.96±17.37]min vs.[87.58±15.99]min,P=0.026),larger CIV([74.00±12.76]ml vs.[24.28±14.72]ml,P＜0.01)and HPV([121.43±22.21]ml vs.[91.62±11.34]ml,P＜0.01),smaller MMR([1.65±0.15]vs.[9.42±1.91],P＜0.01),higher 90-day mRS score([3.60±0.54]score vs.[1.22±0.83]score,P＜0.01),and a significantly different distribution of Tan collateral scores(P＜0.01).(2)Multivariate Logistic regression analysis was performed with futile recanalization as the dependent variable,identified the following independent predictors of futile recanalization:HPV(OR,2.042,95%CI 1.296-3.218,P=0.002),CIV(OR,2.373,95%CI 1.315-4.280,P=0.004),MMR(OR,1.758,95%CI 1.135-2.721,P=0.011),and Tan collateral score(OR,5.166,95%CI 2.100-12.651,P＜0.01).(3)A nomogram prediction model for futile recanalization after MT in ACLVO stroke was constructed based on the four imaging parameters as aforementioned.ROC curve analysis demonstrated that the area under the curve for this model in predicting futile recanalization after MT was 0.846(95%CI 0.739-0.912),with a sensitivity of 0.844 and a specificity of 0.817.The calibration curve and the Hosmer-Lemeshow test indicated the goodness-of-fit was high(P=0.617),and the overall stability of the model was good.Conclusion The predictive model for futile recanalization after MT for acute ACLVO constructed base on HPV,CIV,MMR and Tan collateral score facilitates the identification patients with high-risk of futile recanalization.

Objective To establish a prediction model for futile recanalization after mechanical thrombectomy(MT)in acute anterior circulation large vessel occlusion(ACLVO)stroke patients based on multimodal imaging features,and to evaluate its predictive performance.Methods Retrospectively enrolled consecutive ACLVO patients who underwent MT with successful recanalization(modified thrombolysis in cerebral infarction[mTICI]grade≥2b)at the Department of Neurology of Fuyang People's Hospital between June 2023 and December 2024.Demographic and clinical data were collected,including age,gender,hypertension,diabetes mellitus,atrial fibrillation,smoking history,alcohol consumption history,National Institutes of Health stroke scale(NIHSS)score upon admission,intravenous thrombolysis,wake-up stroke,onset-to-puncture time(OPT),puncture-to-recanalization time(PRT),occlusion vessel(internal carotid artery,middle cerebral artery),treatment method(suction thrombectomy,stent thrombectomy,suction+stent thrombectomy).All patients underwent pre-procedural CT perfusion(CTP)+CT angiography(CTA)of the head and neck.Imaging parameters included hypoperfusion(defined as time to peak＞6 s)volume(HPV),core infarct(defined as cerebral blood flow＜30%)volume(CIV),mismatch ratio(MMR;HPV/CIV),and Tan collateral score(poor collaterals:0-1 score,good collaterals:2-3 score).Patients were followed up at 90 days post-procedure via outpatient clinic or re-admission.Patients with a modified Rankin scale(mRS)score≤2 were classified into the effective recanalization group,while those with mRS score≥3 were classified into the futile recanalization group.Imaging variables with statistically significant differences between the futile recanalization and effective recanalization groups were included in multivariate Logistic regression analysis to identify independent predictors of futile recanalization and construct a nomogram model.The predictive value of the model was assessed using the receiver operating characteristic(ROC)curve.Model calibration was evaluated using the Hosmer-Lemeshow test(goodness-of-fit defined as P＞0.50).Results(1)A total of 105 ACLVO patients with successful MT recanalization were included(65 males,40 females,mean age[66±11]years,ranged 31～87 years).There were 60 patients in the effective recanalization group and 45 in the futile recanalization group.Compared to the effective recanalization group,the futile recanalization group had significantly higher age([69±11]years vs.[63±11]years,P=0.012),higher proportion of diabetes mellitus(33.33%[15/45]vs.16.67%[10/60],P=0.047),higher pre-treatment NIHSS score([15.51±2.73]vs.[13.25±2.71],P＜0.01),longer OPT([516.40±192.48]min vs.[322.98±171.22]min,P＜0.01)and PRT([94.96±17.37]min vs.[87.58±15.99]min,P=0.026),larger CIV([74.00±12.76]ml vs.[24.28±14.72]ml,P＜0.01)and HPV([121.43±22.21]ml vs.[91.62±11.34]ml,P＜0.01),smaller MMR([1.65±0.15]vs.[9.42±1.91],P＜0.01),higher 90-day mRS score([3.60±0.54]score vs.[1.22±0.83]score,P＜0.01),and a significantly different distribution of Tan collateral scores(P＜0.01).(2)Multivariate Logistic regression analysis was performed with futile recanalization as the dependent variable,identified the following independent predictors of futile recanalization:HPV(OR,2.042,95%CI 1.296-3.218,P=0.002),CIV(OR,2.373,95%CI 1.315-4.280,P=0.004),MMR(OR,1.758,95%CI 1.135-2.721,P=0.011),and Tan collateral score(OR,5.166,95%CI 2.100-12.651,P＜0.01).(3)A nomogram prediction model for futile recanalization after MT in ACLVO stroke was constructed based on the four imaging parameters as aforementioned.ROC curve analysis demonstrated that the area under the curve for this model in predicting futile recanalization after MT was 0.846(95%CI 0.739-0.912),with a sensitivity of 0.844 and a specificity of 0.817.The calibration curve and the Hosmer-Lemeshow test indicated the goodness-of-fit was high(P=0.617),and the overall stability of the model was good.Conclusion The predictive model for futile recanalization after MT for acute ACLVO constructed base on HPV,CIV,MMR and Tan collateral score facilitates the identification patients with high-risk of futile recanalization.

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.

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.

Objective To study the effect of low frequency electrical stimulation on blood hormone levels in differ -ent animals.Methods At 12 h, 24 h and 36 h after low frequency electrical stimulation to Chinese tree shrews , Wistar rats, and BALB/c mice, respectively, the blood noradrenaline (NA) and endothelin (ET) levels were determined by ra-dioimmunoassay ( RIA) .Results The blood NA and ET levels of electrical stimulation group were significantly higher than that in the control group (P <0.01).At 24 h after reserpine treatment, the same electrical stimulation was given. The NA, ET levels were significantly decreased compared with that in the electrical stimulation group (P<0.05 to 0.01). Different animals responded to the same electric stimulus differently , following the order of Chinese tree shrews >Wistar rats >BALB/c mice.Conclusions Low frequency electrical stimulation can promote the release of noradrenaline and en -dothelin in Chinese tree shrews , Wistar rats and BALB/c mice.Reserpine can reduce the stress induced by low frequency electric stimulation to the body .

Objective To study the effect of low frequency electrical stimulation on hormone levels in organs of Chinese tree shrews after death.Methods Giving Chinese tree shrews low frequency electrical stimulation.At 0 h, 3 h, 6 h, 12 h, 18 h, 24 h, 36 h and 72 h after death, the thyroid, liver, spleen were taken,and the levels of endothelin (ET), atrial natriuretic factor( ANF) , thromboxane ( TX) were determined by RIA method.At 0 h after death, midbrain ventral tegmental area ( VTA) of Chinese tree shrews was taken to detect the c-fos expression.Results After electrical stimula-tion, ET, ANF, TX levels in the cadaver organs and VTA c-fos expression of Chinese tree shrews were significantly in-creased than in the control group.The contents were decreasing with the time after death.Conclusions Low frequency e-lectrical stimulation can induce the synthesis and release of hormones in organs and c-fos expression in brain tissue of Chi-nese tree shrews.

Objective To study the effects of living environment conditions and animal-animal interaction on the blood hormone levels and psychological behavior in Chinese tree shrews .Methods Chinese tree shrews were raised in ca-ges of different space sizes or were administered reserpine for 15, 30, 60, 120, 180 days, respectively.Then the animals were anesthetized by ether inhalation , and blood samples were taken from the heart to detect the levels of blood testosterone (T), estradiol (E2), endothelin (ET), adrenaline (A) and noradrenaline (NA) by radioimmunoassay (RIA).Results 1.Chinese tree shrews were bred in large cage (D1group) or small cage (X1 group) for 15, 30, 60, 120, 180 days, re-spectively.Compared with the animals bred in the large cage (D1 group), the level of blood testosterone (T) was signifi-cantly reduced (P<0.01), and the levels of adrenaline , noradrenaline and endothelin were significantly increased in the small cage group (P<0.01 for all).2.The animals raised in small cages in close neighborhood with large cages for 15, 30, 60, 120, 180 days, respectively.The levels of testosterone, adrenaline and noradrenaline in the large cage group (X2 group) were significantly higher than those of the small cage group (X1 group) (P<0.01 for all).3.The adrenaline and noradrenaline levels were significantly lower in all the reserpine groups (P<0.01 for all).4.The animals bred in small cages (X1 group) and in small cages in close neighborhood with large cages showed sudden loss , reduced appetite, testicu-lar atrophy , penile prolapse and stress symptoms .The animals of the reserpine groups appeared gentle temperament , signif-icantly reduced activity and reduced appetite .However , after stopping the reserpine administration and feeding them in large cages , the animals gradually returned to normal behavior .Conclusion Both animals living environment conditions and animal-animal interaction may cause changes of blood hormone levels and psychological behavior in Chinese tree shrews.

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.