Intratumoral delivery of a Tim-3 antibody-encoding oncolytic adenovirus engages an effective antitumor immune response in liver cancer.

BACKGROUND AND PURPOSE: The use of oncolytic viruses as a gene therapy vector is an area of active biomedical research, particularly in the context of cancer treatment. However, the actual therapeutic success of this approach to tumor elimination remains limited. As such, the present study was developed with the goal of simultaneously enhancing the antitumor efficacy of oncolytic viruses and the local immune response by combining the Ad-GD55 oncolytic adenovirus and an antibody specific for the TIM-3 immune checkpoint molecule (α-TIM-3). APPROACH AND KEY RESULTS: The results of Virus and cell-mediated cytotoxicity assay, qPCR, and Western immunoblotting showed that Ad-GD55-α-Tim-3 oncolytic adenovirus is capable of inducing α-TIM-3 expression within hepatoma cells upon infection, and Ad-GD55-α-TIM-3 exhibited inhibitory efficacy superior to that of Ad-GD55 when used to treat these tumor cells together with the induction of enhanced intracellular immunity. In vivo experiments revealed that Ad-GD55-α-TIM-3 administration was sufficient to inhibit tumor growth and engage in a more robust local immune response within the simulated tumor immune microenvironment. CONCLUSION AND IMPLICATIONS: These results highlighted the promising therapeutic effects of Ad-GD55-α-TIM-3 oncolytic adenovirus against HCC in vitro and in vivo. As such, this Ad-GD55-α-TIM-3 oncolytic adenovirus may represent a viable approach to the treatment of hepatocellular carcinoma.

Latent period and incubation period with associated factors of COVID-19 caused by Omicron variant / 中华预防医学杂志

Objective: To estimate the latent period and incubation period of Omicron variant infections and analyze associated factors. Methods: From January 1 to June 30, 2022, 467 infections and 335 symptomatic infections in five local Omicron variant outbreaks in China were selected as the study subjects. The latent period and incubation period were estimated by using log-normal distribution and gamma distribution models, and the associated factors were analyzed by using the accelerated failure time model (AFT). Results: The median (Q1, Q3) age of 467 Omicron infections including 253 males (54.18%) was 26 (20, 39) years old. There were 132 asymptomatic infections (28.27%) and 335 (71.73%) symptomatic infections. The mean latent period of 467 Omicron infections was 2.65 (95%CI: 2.53-2.78) days, and 98% of infections were positive for nucleic acid test within 6.37 (95%CI: 5.86-6.82) days after infection. The mean incubation period of 335 symptomatic infections was 3.40 (95%CI: 3.25-3.57) days, and 97% of them developed clinical symptoms within 6.80 (95%CI: 6.34-7.22) days after infection. The results of the AFT model analysis showed that compared with the group aged 18-49 years old, the latent period [exp(β)=1.36 (95%CI: 1.16-1.60), P<0.001] and incubation period [exp(β)=1.24 (95%CI: 1.07-1.45), P=0.006] of infections aged 0-17 years old were prolonged. The latent period [exp(β)=1.38 (95%CI: 1.17-1.63), P<0.001] and the incubation period [exp(β)=1.26 (95%CI: 1.06-1.48), P=0.007] of infections aged 50 years old and above were also prolonged. Conclusion: The latent period and incubation period of most Omicron infections are within 7 days, and age may be a influencing factor of the latent period and incubation period.

Latent period and incubation period with associated factors of COVID-19 caused by Omicron variant / 中华预防医学杂志

Objective: To estimate the latent period and incubation period of Omicron variant infections and analyze associated factors. Methods: From January 1 to June 30, 2022, 467 infected persons and 335 confirmed cases in five local Omicron variant outbreaks in China were selected as the study subjects. The latent period and incubation period were estimated by using log-normal distribution and gamma distribution models, and the associated factors were analyzed by using the accelerated failure time model (AFT). Results: The median (Q1, Q3) age of 467 Omicron infections including 253 males (54.18%) was 26 (20, 39) years old. There were 132 asymptomatic infections (28.27%) and 335 (71.73%) symptomatic infections. The mean latent period of 467 Omicron infections was 2.65 (95%CI: 2.53-2.78) days, and 98% of infections were positive for nucleic acid detection within 6.37 (95%CI: 5.86-6.82) days after infection. The mean incubation period of 335 symptomatic infections was 3.40 (95%CI: 3.25-3.57) days, and 97% of them developed clinical symptoms within 6.80 (95%CI: 6.34-7.22) days after infection. The results of the AFT model analysis showed that compared with the group aged 18~49 years old, the latent period [exp(β)=1.36 (95%CI: 1.16-1.60), P<0.001] and incubation period [exp(β)=1.24 (95%CI: 1.07-1.45), P=0.006] of infections aged 0~17 year old were also prolonged. The latent period [exp(β)=1.38 (95%CI: 1.17-1.63), P<0.001] and the incubation period [exp(β)=1.26 (95%CI: 1.06-1.48), P=0.007] of infections aged 50 years old and above were also prolonged. Conclusion: The latent period and incubation period of most Omicron infections are within 7 days, and age may be the influencing factor of the latent period and incubation period.

Construction of AQHI based on joint effects of multi-pollutants in 5 provinces of China / 环境与职业医学

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO2, NO2, CO, PM2.5, PM10, and maximum 8 h O3 concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM2.5, NO2, SO2, and O3 were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM2.5, NO2, SO2 and O3 were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

The Role of Chemokine IL-7 in Tumor and Its Potential Antitumor Immunity.

Interleukin-7 (IL-7) is a cytokine belonging to the chemokine family. It plays a key role in the differentiation, development, and maturation of T lymphocytes and B lymphocytes, which is pivotal to adaptive immunity. In addition to its role in lymphocyte development, recent studies have indicated the antitumor functions of IL-7 in the tumor microenvironment. In this review, we discuss the role of IL-7 in tumors and summarize its antitumor potential and clinical application in lymphoma, leukemia, breast cancer, colon cancer, and so on. Furthermore, the combinational strategies of IL-7 and other antitumor drugs have been also discussed.

The Roles of Mesenchymal Stem Cells in Gastrointestinal Cancers.

Mesenchymal stem cells (MSCs) were reported to have strong immunomodulatory ability, and inhibit the proliferation of T cells and their immune response through cell-to-cell interactions and the generation of cytokines. With high differentiation potential and self-renewal ability, MSCs are considered to function in alleviating inflammatory responses, promoting tissue regeneration and inhibiting tissue fibrosis formation. As the most common malignancies, gastrointestinal (GI) cancers have high incidence and mortality. The accurate diagnosis, exact prognosis and treatment of GI cancers have always been a hot topic. Therefore, the potential applications of MSCs in terms of GI cancers are receiving more and more attention. Recently, there is increasing evidence that MSCs may serve as a key point in the growth, metastasis, inhibition, treatment and prognosis of GI cancers. In this review, we summarized the roles of MSCs in GI cancers, mainly focusing on esophageal cancer (EC), gastric cancer (GC), liver cancer (LC), colorectal cancer (CRC) and pancreatic cancer. Besides, we proposed MSCs as potential targets and treatment strategies for the effective treatment of GI cancers, which may provide better guidance for the clinical treatment of GI cancers.

Apigenin inhibits liver fibrosis through PDK1/AKT signaling pathway in mice / 中国药理学通报

Aim To evaluate the therapeutic effect of apigenin on liver fibrosis in mice anrl the pharmacologi¬cal mechanism.Methods Carbon tetrachloride ( CC14) -induced liver fibrosis mouse model was estab¬lished.The mice were divided into six groups of con¬trol, model, silibinin(55 mg • kg 1 • d 1 ) , apigenin in high dosage (60 mg • kg 1 • d 1 ) , apigenin in mid¬dle dosage( 30 mg • kg 1 • d 1 ) and apigenin in low dosage( 15 mg • kg 1 • d 1 ).The general life status, body weight and liver coefficient of the mice in every group were recorded.HE staining, Masson staining, immunohistochemistry and Western blot were used to e- valuate the effect of apigenin on the pathological chan¬ges, the markers related to epithelial-mesenchymal transition and signaling pathways of liver tissues.Re¬sults In CCI4-induced liver fibrosis mice, middle and high-dosage of apigenin could improve the general life status, increase body weight, decrease liver coeffi¬ cient, and significantly improve liver lesions.Middle and high-dosage of apigenin significantly increased the expression of the epithelial marker protein E-cadherin and significantly decreased the expression of the mes¬enchymal marker protein Vimentin in liver tissues of mice with the disease.The further results showed that middle and high-dosage apigenin could significantly in¬hibit the expression of phosphorvlated PDK1 and phos- phorvlated AKT protein in liver tissues of model mice.Conclusions Apigenin can inhibit EMT by inhibiting PDK1/AKT signaling pathway, which plays an anti-fi- brosis role.The apigenin has the potential to be further developed as a drug to protect the liver and treat liver fibrosis.

Simple Test for Evaluating Hand Function for Chinese / 中国康复理论与实践

Objective:To observe the measurement of Simple Test for Evaluating Hand Function (STEF) in Chinese, and compared to that of Japanese. Methods:From May to June, 2020, 130 healthy individuals were tested with the toolkit and instructions of STEF, and the result was compared with Japanese data with one-sample t-test, and adjusted. Results:Among the ten items performed on the right side of the STEF, nine items, except item four (middle-sized cubes), were significantly different from those of Japanese (|t| > 1.760, P < 0.05). Among the ten items performed on the left side of STEF, seven items, except item four (middle-sized cubes), item seven (vinyl sheets) and item eight (iron circular plates), were significantly different from those of the Japanese (|t| > 2.257, P < 0.001). Conclusion:There is significant difference in the test results of STEF between Chinese and Japanese samples, and need to be adjusted.

Effect of Individualized Occupational Therapy on Occupational Performance of Patients with Schizophrenia / 中国康复理论与实践

Objective:To explore the effect of individualized occupational therapy on occupational performance of schizophrenic patients. Methods:From 2016 to 2018, 30 schizophrenic patients hospitalized over one year in Beijing Anding Hospital were randomly divided into control group (n = 15) and experimental group (n = 15). The control group was given routine group work activities, and the experimental group was given individualized occupational therapy, 30 minutes a time, once a day, five days a week for four weeks. The Comprehensive Occupational Therapy Evaluation Scale (COTE) was used to evaluate the occupational performance of schizophrenic patients before and after treatment。 Results:The difference value of COTE score was higher in the experimental group than in the control group (t = 3.842, P < 0.01), especially for interpersonal communication behavior and task behavior (t > 3.106, P < 0.01). Conclusion:Individualized occupational therapy could improve the occupational performance of patients with schizophrenia.

Application of Functional Near-infrared Spectroscopy in Brain Area Activation Research: Dominant and Non-dominant Hand under Active Grasp-release Task / 中国康复理论与实践

Objective:To apply functional near-infrared spectroscopy (fNIRS) to analyze brain activity pattern of bilateral sensorimotor cortex (SMC) and premotor cortex (PMC) during complex dominant and non-dominant hand movement in healthy subjects. Methods:From August to December, 2019, 15 right-handed healthy residents were recruited. The block designed grip-release task was used in the subjects, and detected oxyhemoglobin and deoxyhemoglobin concentration with fNIRS to analyze the activation of bilateral SMC, PMC and prefontal cortex in term of activation channels and intensity. Results:For the oxyhemoglobin concentration, the number of activated channels was the same in both hemispheres during right (dominant) hand movement, and the activation of left SMC was stronger (P < 0.05); however, more channels were activated in the right hemisphere during left (non-dominant) hand movement, and the activation of right SMC was stronger (P < 0.05). For the deoxyhemoglobin concentration, more channels were activated in the contralateral hemisphere during either dominant or non-dominant hand movement, and the activation of left SMC, Channel 12 (left PMC) and Channel 26 (right PMC) were stronger during right (dominant) hand movement (P < 0.05). Conclusion:It is feasible to use fNIRS to study the activation of hand movement related brain regions during complex movement of dominant and non-dominant hand, especially with the results of oxyhemoglobin concentration.

Study on nutritional risk and nutritional support in patients with liver cancer during perioperative period / 中国医师进修杂志

Objective:To study the nutritional risk and nutritional support in patients with liver cancer during perioperative period.Methods:In Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical, the clinical data of 507 liver cancer patients who underwent surgery College from January 2019 to January 2020 were retrospectively analyzed. The perioperative nutrition was assessed by nutritional risk screening 2002 (NRS 2002), ≥3 scores was diagnosed nutritional risk, and the nutritional support was counted.Results:Among 507 patients, 82 cases (16.2%) had nutritional risk. There was no statistical difference in rate of nutritional risk between male and female: 15.3% (58/379) vs. 18.8% (24/128), χ2 = 0.838, P>0.05. There was no statistical difference in rate of nutritional risk between primary liver cancer patients and secondary liver cancer patients: 18.0% (63/350) vs. 12.1% (19/157), χ2 = 2.781, P>0.05. The rate of nutritional risk in ≥ 60 years old patients was significantly higher than that in <60 years old patients: 25.9% (62/239) vs. 7.5% (20/268), and there was statistical difference ( χ2 = 31.819, P<0.01). The age, incidence of dystrophy and rate of nutritional support before surgery in patients with nutritional risk were significantly higher than those in patients without nutritional risk: (65.3 ± 12.7) years old vs. (55.9 ± 8.9) years old, 13.4% (11/82) vs. 0 and 24.4% (20/82) vs. 2.6% (11/425), and there were statistical differences ( P<0.01); there were no statistical differences in sex composition, tumor origin, rate of nutritional support after surgery and albumin between patients with nutritional risk and patients without nutritional risk ( P>0.05). Among 31 nutritional support patients before surgery, parenteral nutrition (PN) was in 1 case, enteral nutrition (EN) was in 30 cases; among 453 nutritional support patients after surgery, PN was in 297 cases, EN was in 27 cases, and PN + EN was in 129 cases. Conclusions:The incidence of nutritional risk in patients with liver cancer during perioperative period is high, and especially elderly patients should pay attention to nutritional support. NRS 2002 is a powerful tool and should be recommended to use at patients with liver cancer, and provide the evidence of nutritional therapy.

Absolute bioavailability of salidroside in Beagle dog / 药学实践杂志

Objective To develop a HPLC-MS/MS method for the absolute bioavailability study of salidroside in Beagle dogs. Methods Gastrodin was used as internal standard. Plasma samples were treated by protein precipitation and separated by Symmetry RP18 column (100 mm×4.6 mm, 3.5 μm). 0.1% formic acid in water(A) and 0.1% formic acid in acetonitrile: methanol (20 : 80, V/V) (B) were used as the mobile phase for isocratic elution with 35% mobile phase B. The flow rate was 0.4 ml/min. Column temperature was 40 ℃. Injection volume was 2 μl. By electrospray ionization source (ESI) and multi-reaction monitoring (MRM) mode, the MRM ion pairs of salidroside and gastrodin were identified as m/z 299.1→118.9 and m/z 285.1→122.9, separately. Blood samples were collected at different time points after oral or intravenous administration of salidroside. The harvested plasma samples were analyzed by HPLC-MS/MS method to assess the pharmacokinetics and absolute bioavailability of salidroside. Results Excellent linearity(r>0.998 6) was found in the concentration range of 10−10 000 ng/ml for salidroside and the lowest quantitative concentration was 10 ng/ml. The recovery was 89.5%−91.8%. The intra-day precision (RSD) was less than 9.7%, and the inter-day precision (RSD) was less than 7.3%. After a single oral dose of 15 mg/kg or an intravenous injection of 1.5 mg/kg of salidroside, cmax was (9 680±3725) and (9 310±1 645) ng/ml; tmax was (1.25±0.67) and (0.011±0.017) h, AUC0−t was (20 535.4±5 200.0) and (4 646.7±720.5) ng·h/ml, AUC0−∞ was (20 607.9±5 266.2) and (4 691.6±715.2) ng·h/ml; t1/2 was (1.31±0.63) and (0.98±0.13) h, respectively. Conclusion The LC-MS/MS method established in this study was simple, rapid, sensitive and reliable. It meets the regulatory requirements of biological analysis for pharmacokinetic properties of salidroside in Beagle dogs. The absolute bioavailability of salidroside in Beagle dogs is (43.9±11.2)%.

Interactive effects of fine particulate matter and temperature on residents mortality in Pudong, Shanghai / 上海预防医学

Objective To evaluate the interactive effects of fine particulate matter and temperature on non-accidental mortality of residents in Pudong, Shanghai. Methods Daily mortality, air pollutants and meteorological data from Jan 1st.2016 to Dec 31st.2017 were collected.Generalized additive Poisson regression models was used to estimate the effects of PM2.5 pollution on daily mortality, bivariate response surface models and temperature stratified models were applied to examine the interaction of temperature with PM2.5 on mortality. Results A total of 43 345 non-accidental deaths were included, daily mean PM2.5 concentration was 39.1 μg/m3, daily mean temperature was 17.7 ℃.A 10 μg/m3 increase in the daily PM2.5 at lag 1 day was associated with a 0.56%(95%CI:0.11%-1.01%), 0.49%(95%CI:-0.19%-1.18%) and 0.22%(95%CI:-1.14%-1.60%) increase in non-accidental, cardiovascular and respiratory mortality, respectively.Higher risks were identified for males and the older (≥65 years).The effect estimates per 10 μg/m3 increase in PM2.5 in medium temperature level were 0.59%(95%CI:0.04%-1.14%)for non-accidental, 0.51%(95%CI:-0.32%-1.35%)for cardiovascular and 0.51%(95%CI:-0.32%-1.35%) for respiratory mortalities.The PM2.5 effects were approximately 2-4 times higher in higher temperature level for non-accidental and cardiovascular mortalities compared with other temperature levels; for respiratory mortality, the PM2.5 effects was approximately 2-fold higher in lower temperature levels than the medium, although the interactions between temperature and PM2.5 were statistically insignificant. Conclusions Temperature may modify the effects of PM2.5 on mortality in Pudong, Shanghai and the interactive pattern may be different across disease-specific mortalities.

Effect of electroacupuncture on expressions of acetylcholine and mucin 5AC in the lungs of rats with chronic obstructive pulmonary disease / 针灸推拿医学（英文版）

Objective:To observe the effect of electroacupuncture (EA) on the expressions of acetylcholine (ACh) and mucin 5AC (MUC5AC) in the lungs of rats with chronic obstructive pulmonary disease (COPD),and explore the mechanism of EA in treating COPD.Methods:Thirty Sprague-Dawley (SD) rats were randomly divided into a control group,a COPD group,and an EA group,with 10 rats in each group.The control group was a group of normal rats.The COPD rat model was induced by cigarette smoke combined with lipopolysaccharide (LPS).The COPD rats were treated with EA at bilateral Feishu (BL 13) and Zusanli (ST 36) in the EA group,30 min each time,once a day,successively for 14 d.The lung function was tested.The contents of ACh and MUC5AC in lungs and bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA).Pearson method was used to analyze the correlation between pulmonary function and the content of MUC5AC in lungs.The mRNA and protein expressions of MUC5AC in lung tissues were detected by real-time polymerase chain reaction (RT-PCR) and Western blot (WB),respectively.The immune response of MUC5AC was observed by immunohistochemistry.Results:Eight rats were left in each group,and the other two died.Compared with the control group,the total airway resistance (Raw) increased significantly and dynamic compliance (Cdyn) decreased significantly in the COPD group (P＜0.01);compared with the COPD group,the Raw level declined significantly and Cdyn increased significantly in the EA group (P＜0.01).The contents of ACh and MUC5AC in the lungs and BALF were remarkably higher in the COPD group compared with those in the control group (P＜0.01,P＜0.001);compared with the COPD group,the contents of ACh and MUC5AC were significantly lower in the EA group (P＜0.05,P＜0.001).There was a negative correlation between MUC5AC content and lung function (P＜0.001).The mRNA and protein expressions of MUC5AC in the lungs were significantly higher in the COPD group than in the control group (P＜0.001);compared with the COPD group,the expressions were significantly lower in the EA group (P＜0.01).Compared with the control group,the immune response of MUC5AC in the airway epithelium significantly increased in the COPD group (P＜0.001);the immune response of MUC5AC was significantly lower in the EA group compared with that in the COPD group (P＜0.001).Conclusion:EA treatment can improve the lung function of COPD rats,which may be related to its effect in the down-regulation of ACh and MUC5AC contents in the lungs as well as the inhibition of mucus hypersecretion.

The features of idiopathic membranous nephropathy in elderly patients and its correlation with the expression of the expression of phospholipase A2 receptor / 中华老年医学杂志

Objective To investigate the clinico-pathological features of idiopathic membranous nephropathy (IMN ) and the expression of phospholipase A2 receptor (PLA2R ) in elderly patients. Methods A total of 109 elderly patients with IMN confirmed by renal biopsy at Wuxi People's Hospital from July 2008 to February 2015 were included.Data were retrospectively collected. Results (1)Participating patients with IMN had a mean age of (67.3 ± 5.4)years ,and 67.9% of them had hypertension and 65.1% had nephrotic syndrome.Compared with non-elderly patients ,elderly patients had a higher proportion with hypertension (67.9% vs.25.2%)(P＝0.000) ,higher systolic pressure[(143.1 ± 15.2)mmHg vs. (127.3 ± 13.3)mmHg](P＝ 0.000) ,higher diastolic pressure [(88.4 ± 10.0)mmHg vs. (80.2 ± 8.4)mmHg](P＝ 0.000) ,more severe tubulointerstitial lesions [(3.1±1.9)points vs.(2.0±1.9)points](P＝0.000),and lower eGFR[(70.9±22.9)ml·min－1· 1.73 m －2vs. (90.6 ± 27.1 ) ml·min－1·1.73 m －2] ( P ＝ 0.000 ). (2 ) There were more severe tubulointerstitial lesions[(4.7 ± 1.8)points vs. (2.4 ± 1.7)points ,2.9 ± 1.6 points](P ＝ 0.000 , 0.000)and lower eGFR[(50.4 ± 17.4)ml·min－1·1.73 m －2vs. (80.3 ± 19.7)ml·min－1·1.73 m －2, (72.3 ± 21.4)ml·min－1·1.73 m －2](P＝0.000 ,0.000)in elderly patients of pathological stage Ⅱ, compared with patients of pathological stages Ⅰ and Ⅰ-Ⅱ. (3)The rate of positive PLA2R was 82.4%.Patients with positive PLA2R had higher proteinuria[(4.5 ± 2.3)g vs. (2.9 ± 1.1)g](P＝0.042) ,lower eGFR[(66.8 ± 21.8)ml·min－1·1.73 m －2vs. (97.7 ± 16.0)ml·min－1·1.73 m －2](P＝0.000) ,and more severe tubulointerstitial lesions [(3.1 ± 2.0)points vs. (1.7 ± 1.1)points](P＝0.037)than patients with negative PLA2R. (4)Multiple regression analysis showed that PLA2R positive rate(P＝0.008) ,tubulointerstitial lesion(P＝0.000) ,and level of cholesterol(P＝0.025)were negatively correlated with eGFR (R2＝0.572). Conclusions Compared with non-elderly patients , elderly patients with IMN have poorer prognosis as a result of higher blood pressure and more severe tubulointerstitial lesions.Elderly patients with IMN of advanced pathological stages and positive PLA2R have more severe kidney injury and tubulointerstitial lesions ,resulting in poor prognosis.

Establishment and application of light initiated chemiluminescence assay of high mobility group box 1 / 中华核医学与分子影像杂志

Objective To establish a fast and quantitative light initiated chemiluminescent assay (LICA) method for high mobility group box1 (HMGB1) determination.Methods Two strains of paired HMGB 1 monoclonal antibodies were used.One was used to coat receptor microspheres.The other was labeled with biotin first and then composed with chain mildew element of affinity donor microsphere to form LICA method for HMGB1.After optimizing the reaction system,the technical specifications of the method was evaluated.Serum HMGB1 levels of common pneumonia patients (CPP) and severe pneumonia patients (SPP) were measured and compared with that of health controls.Two-sample t test was used.Results The sensitivity of LICA was 0.1 μg/L,with linear measurement ranging from 0.1 to 1 000 μg/L.The precisions of intra-and inter-analysis were 1.74％-2.92％ and 1.93％-3.73％ respectively,both were lower than 5％.The recovery rate was 99.74％ (range:94.53％-106.37％).The correlation coefficient of LICA and enzyme-linked immunosorbent assay (ELISA) was 0.888 2.The LICA method had good specificity and no obvious cross reaction with HMGB2 and HMGB3.The serum HMGB1 level in CPP (n=35) and SPP (n=25) was significantly higher than that in health controls (n=35):(6.76±3.13),(19.69±+9.04) vs (1.49±+0.74) μg/L;t values:-5.447 and-5.186,both P＜0.01.The HMGB1 levels between CPP and SPP were also significantly different (t=-3.500,P＜0.01).Conclusions The established LICA method of HMGB1 has high sensitivity and specificity with reliable results.This method is also homogeneous,fast and cleaning-free,thus has a good prospect in clinical application.

Dual-antigen sandwich-type time-resolved fluoroimmunoassay for phospholipase A2 receptor antibody, a new marker of membranous nephropathy / 中华核医学与分子影像杂志

Objective To establish a time-resolved fluoroimmunoassay (TRFIA) method for detecting M-type phospholipase A2 receptor (PLA2R) antibody and to investigate the diagnostic value of serum PLA2R antibody for idiopathic membranous nephropathy (IMN).Methods The microplates coated with recombined PLA2R antigen and Eu3+-streptavidin labeled PLA2R antigen were used to establish a dual-antigen sandwich-type TRFIA for PLA2R antibody detection (anti-PLA2R-TRFIA).The serum concentrations of PLA2R antibody in 63 IMN patients (36 males,27 females,age 25-75 years) and 90 healthy volunteers (30 males,60 females,age 22-53 years) were quantitatively analyzed.Kruskal-Wallis H test and MannWhitney u test were used to analyze the data.Results The range of anti-PLA2R-TRFIA was 0-10 mg/L and the sensitivity was 5 μg/L,while ED20,ED50 and ED80 of the standard curve were (0.144±0.012),(0.707±0.029) and (3.466±0.098) mg/L,respectively.The CV of inter-and intra-assay were 4.7％ and 5.1％,respectively.The average concentration of serum PLA2R antibody in healthy volunteers was 0.455(0.320,0.593) mg/L,but in IMN patients it was 2.690(0.717,7.750) mg/L (z=-3.688,P＜0.05).Meanwhile,the serum levels of PLA2R antibody in IMN patients were significantly different between different stages and ages (x2 values:10.328,9.716,both P＜0.05).According to the receiver operating characteristic (ROC) curve,when the diagnostic cut-off was set at 0.80 mg/L for IMN detection,the sensitivity and specificity of anti-PLA2R-TRFIA were 73.0％ (46/63) and 95.6％ (86/90),respectively.Conclusions AntiPLA2R-TRFIA has been well established.This quick and easy-performance method could increase the diagnostic accuracy for IMN.

Establishment of a time-resolved fluoroimmunoassay in detection of human epidermal growth factor receptor 2 / 中华核医学与分子影像杂志

Objective To set up a time-resolved fluoroimmunoassay (TRFIA) method for human epidermal growth factor receptor 2 (HER2) detection and to evaluate its performance.Methods Each well of the 96-microwell plate was coated with monoclonal antibody of HER2(H7) and another monoclonal antibody of HER2(E5) was labeled by Eu3+.The sensitivity,stability,specificity,measurement range and reference value of this method were tested.The correlation between chemiluminescence (CLIA) method and TRFIA method was analyzed.Results The sensitivity of HER2-TRFIA method was 0.214 ng/ml.The measurement range was 0.214-1 000 ng/ml.The mean within-run CV and mean between-run CV were 3.48％ and 4.13％,respectively.HER2-TRFIA method had no cross-reaction with HER1 and its reference range was 0-13.20 ng/ml.The correlation coefficient between TRFIA and CLIA was 0.997.The same batch of reagents were found to be stable for more than 6 months at 4 ℃.Conclusions HER2-TRFIA method has high sensitivity,specificity,stability and wide detecting range.It might be suitable for clinical use.

Simultaneous detection of tumor markers in human serum using time-resolved fluorescence microspheres immunochromatographic assay / 中华核医学与分子影像杂志

Objective To develop a time-resolved fluorescent microspheres immunochromatographic assay (TRFMIA) for detection of alphafetoprotein (AFP) and carcinoembryonic antigen (CEA) in human serum and to evaluate its performance.Methods The Eu-time-resolved fluorescent polystyrene particles conjugated with monoclonal antibody AC18# for AFP and AE03# for CEA were used as fluorescent labels.The monoclonal antibody AC17# for AFP,AE05# for CEA and goat anti-rabbit antibody were immobilized on the nitrocellulose membrane as the test lines and control line.Several performances indicators were measured,including linear range,detection limit,and specificity.AFP and CEA were measured by the new method and the results were compared with those obtained by time-resolved fluoroimmunoassay (TRFIA) and electro-chemiluminescence immunoassay (ECLIA) using linear correlation analysis.Results The measurement ranges of AFP were 0.07-1 000.00 kU/L with the intra-and inter-assay CV of 5.93％ and 11.07％,and those of CEA were 0.12-500.O0 μg/L with the intra-and inter-assay CV of 7.53％ and 12.13％ respectively.The average recovery rate of AFP and CEA was 92.77％ and 94.73％,respectively.Measurements obtained by TRFMIA had strong correlation coefficients ranging from 0.93 to 0.97 when compared with those obtained by TRFIA and ECLIA.Conclusion TRFMIA,which can simultaneously detect AFP and CEA,has been successfully established.

Quantitation of CA199 based on Magnetic Microspheres time resolved fluoroinnnunoassay technology / 国际检验医学杂志

Objective To establish the time-resolved fluoroimmunoassay(TRFIA)of CA199 based on Mag-netic Microspheres(Nano-TRFIA).Methods Based on a sandwich-type immunoassay format,analytes in sam-ples were captured by magnetic particles coated with anti-CA199 antibody B1 and"sandwiched"by anti-CA199 antibody B7 labeled with europium chelates.A total of 90 serum samples were analysed by this new method. Results The sensitivity was 0.2 U/mL,the intra.and inter.assay CV of the Nano-TRFIA were 4.84% and 8.32% respectively,and the average recovery rate was 97.91%.The cross-reacting rates with alpha fetopro-tein and CA125 were negligible.The labeled B1 with Magnetic Microspheres was at least stable for three months at 4 ℃.Serum samples from patients and healthy blood donors were analyzed,the linear correlation of TRFIA and ECLIA measurements was positive(Y = 0.969 8X+ 4.015 3).As the gold standard of ECLIA, Nano-TRFIA had two false positive.Conclusion The newly developed Nano-TRFIA based on Magnetic Mi-crospheres technique was highly sensitive,stable and specific in the immuno-determination of serum CA199. The results showed that the methods of Nano-TRFIA based on Magnetic Microspheres could be used for the clinic.