Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Objective To carry out a proficiency testing of content determination of geniposide in Gardeniae fructus,evaluate the content determination ability of index components in traditional Chinese medicine in the laboratory of inspection and detection in drug-related fields,and improve the quality control ability of content determination of related laboratories.Methods The laboratory's capability-verification activities were conducted based on the CNAS-RL02 Rules for Proficiency Testing and ISO/IEC 17043 Conformity Assessment-General Requirements for Proficiency Testing.After preparing the sample,the results of homogeneity and stability tests were analyzed according to CNAS-GL003 Guidance on Evaluating the Homogeneity and Stability of Samples Used for Proficiency Testing.After the test results were qualified,they were used as proficiency testing samples and randomly distributed to participants.The results were collected,and the robust statistical method and the Z scores were used to analyze the results of these laboratories'reports.Results 403 laboratories in this proficiency testing program reported the results,of which 367 results were acceptable,accounting for 91.07％,17(4.22％)laboratories obtained suspicious results,and 19 laboratories gave unsatisfactory results,with the dissatisfaction rate of 4.71％.Conclusion The majority of the 403 participant laboratories have the ability to determine the content of geniposide in Gardeniae fructus by HPLC and the laboratory testing ability and quality management level of the drug monitoring system are high.This proficiency testing provides a basis for understanding the technical reserve capacity and management level of China's pharmaceutical inspection and testing laboratories,and provides technical support for future government supervision.

Antibodies, Antinuclear ; Autoantibodies ; China ; Cohort Studies ; Humans ; Scleroderma, Systemic

Objective:To explore the clinical effect of Pingchuan Decoction combined with routine western medicine therapy in the treatment of acute attack of bronchial asthma in children. Methods:From January 2017 to June 2019, 118 children with acute attack of bronchial asthma were selected from the Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and they were randomly divided into control group (59 cases) and observation group (59 cases) according to the random number table. The control group was treated with routine western medicine therapy, and the observation group was treated with Pingchuan Decoction on the base of control group, and both groups were treated for 14 days. The main symptom scores before and after treatment were evaluated. The percentage of forced vital capacity expressed as percent predicted (FVC% pred) and the forced expiratory volume in 1 second expressed as percent predicted (FEV1% pred) were measured by pulmonary function meter. The levels of CD3 +, CD4 + and CD4 +/CD8 + in peripheral blood were detected by flow cytometry. The adverse reactions during the treatment were recorded and the clinical efficacy was evaluated. Results:The total clinical effective rate was 93.2% (55/59) in the observation group and 71.2% (42/59) in the control group, where the difference between the two groups was statistically significant ( χ2=9.790, P=0.002). After treatment, the scores of cough, wheezing and wheezing rale in the observation group were significantly lower than those in the control group ( t=27.695, 17.573, 32.827, P<0.001). After treatment, FVC% pred [(80.21 ± 4.06)% vs. (71.71 ± 3.95)%, t=11.526], FEV1% pred [(78.84±3.92)% vs. (72.26 ± 3.59)%, t=9.508] in the observation group were significantly higher than those in the control group ( P<0.01). The levels of CD3 + [(74.05 ± 5.13)% vs. (67.44 ± 4.98)%, t=7.101], CD4 + [(48.43 ± 4.31)% vs. (42.20 ± 4.06)%, t=8.082] and the ratio of CD4 +/CD8 + (1.67 ± 0.29 vs. 1.34 ± 0.25, t=6.620) in the observation group were significantly higher than those in the control group ( P<0.01). During the treatment, the incidence of adverse reactions was 10.2% (6/59) in the observation group and 6.8% (4/59) in the control group, and there was no significant difference between the two groups ( χ2=0.437, P=0.509). Conclusion:The Pingchuan Decoction combined with routine western medicine therapy can reduce the clinical symptoms of children with acute attack of bronchial asthma, improve lung function, improve organism immunity and clinical effect with safety.

The epidemic of coronavirus disease 2019 (COVID-19) puts higher demands on critical care medicine. Lots of studies have been conducted to solve COVID-19-related problems. Therefore, we reviewed the annual progress for COVID-19-related issues including antivirals threapies, respiratory support and immunomodulatory therapies and other critical issues, including the effect of antibiotic on mitochondrial damage and its relationship with sepsis, the goal and direction of antimicrobial de-escalation, drug prophylaxis of constipation, bleeding in gastrointestinal disorders and management of critical illness in the informalization era and so on. We hope to provide reference for clinical and scientific research work of the intensivists.

Objective:To construct a real-time monitoring system based on computer vision for monitoring withdrawal speed of colonoscopy and to validate its feasibility and performance.Methods:A total of 35 938 images and 63 videos of colonoscopy were collected in endoscopic database of Renmin Hospital of Wuhan University from May to October 2018. The images were divided into two datasets, one dataset included in vitro, in vivo and unqualified colonoscopy images, and another dataset included ileocecal and non-cecal area images. And then 3 594 and 2 000 images were selected respectively from the two datasets for testing the deep learning model, and the remaining images were used to train the model. Three colonoscopy videos were selected to evaluate the feasibility of real-time monitoring system, and 60 colonoscopy videos were used to evaluate its performance.Results:The accuracy rate of the deep learning model for classification for in vitro, in vivo, and unqualified colonoscopy images was 90.79% (897/988), 99.92% (1 300/1 301), and 99.08% (1 293/1 305), respectively, and the overall accuracy rate was 97.11% (3 490/3 594). The accuracy rate of identifying ileocecal and non-cecal area was 96.70% (967/1 000) and 94.90% (949/1 000), respectively, and the overall accuracy rate was 95.80% (1 916/2 000). In terms of feasibility evaluation, 3 colonoscopy videos data showed a linear relationship between the retraction speed and the image processing interval, which indicated that the real-time monitoring system automatically monitored the retraction speed during the colonoscopy withdrawal process. In terms of performance evaluation, the real-time monitoring system correctly predicted entry time and withdrawal time of all 60 examinations, and the results showed that the withdrawal speed and withdrawal time was significantly negative-related ( R=-0.661, P<0.001). The 95% confidence interval of withdrawal speed for the colonoscopy with withdrawal time of less than 5 min, 5-6 min, and more than 6 min was 43.90-49.74, 40.19-45.43, and 34.89-39.11 respectively. Therefore, 39.11 was set as the safe withdrawal speed and 45.43 as the alarm withdrawal speed. Conclusion:The real-time monitoring system we constructed can be used to monitor real-time withdrawal speed of colonoscopy and improve the quality of endoscopy.

Objective:To construct an artificial intelligence-assisted diagnosis system to detect gastric ulcer lesions and identify benign and malignant gastric ulcers automatically.Methods:A total of 1 885 endoscopy images were collected from November 2016 to April 2019 in the Digestive Endoscopy Center of Renmin Hospital of Wuhan University. Among them, 636 were normal images, 630 were with benign gastric ulcers, and 619 were with malignant gastric ulcers. A total of 1 735 images belonged to training data set and 150 images were used for validation. These images were input into the Res-net50 model based on the fastai framework, the Res-net50 model based on the Keras framework, and the VGG-16 model based on the Keras framework respectively. Three separate binary classification models of normal gastric mucosa and benign ulcers, normal gastric mucosa and malignant ulcers, and benign and malignant ulcers were constructed.Results:The VGG-16 model showed the best ability of classification. The accuracy of the validation set was 98.0%, 98.0% and 85.0%, respectively, for distinguishing normal gastric mucosa from benign ulcers, normal gastric mucosa from malignant ulcers, and benign ulcers from malignant ulcers.Conclusion:The artificial intelligence-assisted diagnosis system obtained in this study shows noteworthy ability of detection of ulcerous lesions, and is expected to be used in clinical to assist doctors to detect ulcer and identify benign and malignant ulcers.

Objective:To establish a deep convolutional neural network (DCNN) model based on YOLO and ResNet algorithm for automatic detection of colorectal polyps and to test its function.Methods:Colonoscopy images and videos collected from the database of Digestive Endoscopy Center of Renmin Hospital of Wuhan University from January 2018 to March 2019 were divided into three databases (database 1, 3, 4). The public database CVC-ClinicDB (composed of 612 polyp images extracted from 29 colonoscopy videos provided by Barcelona Hospital, Spain) was used as the database 2. Database 1 (4 700 colonoscopy images from January 2018 to November 2018, including 3 700 intestinal polyp images and 1 000 non-polyp images) was used for establishing training and verifying the DCNN model. Database 2 (CVC-ClinicDB) and database 3 (720 colonoscopy images from January 2019 to March 2019, including 320 intestinal polyp images and 400 non-polyp images) were used for testing the DCNN model on image detection. Database 4 (15 colonoscopy videos in December 2019, containing 33 polyps) was used for testing the DCNN model on video detection. The sensitivity, specificity, accuracy and false positive rate of the DCNN model for detecting intestinal polyps were calculated.Results:The sensitivity of the DCNN model for detecting intestinal polyps in database 2 was 93.19% (602/646). In database 3, the DCNN model showed the accuracy of 95.00% (684/720), sensitivity of 98.13% (314/320), specificity of 92.50% (370/400), and false positive rate of 7.50% (30/400) for detecting intestinal polyps. In database 4, the DCNN model achieved a per-polyp-sensitivity of 100.00% (33/33), a per-image-accuracy of 96.29% (133 840/138 998), a per-image-sensitivity of 90.24% (4 066/4 506), a per-image-specificity of 96.49% (129 774/134 492), and a per-image-false positive rate of 3.51% (4 718/134 492).Conclusion:The DCNN model constructed in the study has a high sensitivity and specificity for automatic detection of colorectal polyps both in the colonoscopy images and videos, has a low false positive rate in the videos, and has the potential to assist endoscopists in diagnosis of colorectal polyps.

Objective To discuss the clinical effect of different scaffold in pulp vascular regeneration . Methods 22 young permanent teeth with periapical lesions were randomly divided into observation group and control group,11cases in each group .After the disinfection protocol was completed , the apexes of the control group were irritated to initiate bleeding to produce a blood clot to achieve pulp revascularization ,while the observation group used platelet rich plasma as physical scaffold to operate pulp revasculrization .Results In the control group , the two patients showed painful tooth at 1 and 8 months,the three patients showed healed periapical lesions and narrowed apical foramen at 12 and 18 months ,the six patients showed healed periapical lesions and closure of the apical fora -men at 12 and 18 months.In the observation group ,the three patients showed painful tooth at 1,3 and 8 months,the four patients showed healed periapical lesions and narrowed apical foramen at 12 and 18 months,the four patients showed healed periapical lesions and closure of the apical foramen at 12 and 18 months.There was no statistically significant difference between the observation group and control group by Fisher's exact probabilities (P=1.000). Conclusion Platelet rich plasma is potentially an ideal scaffold for pulp revascularization .

Objective:To investigate the role and mechanism of leptin on dendritic cells by NLRP3 inflammasome.Methods: BMDCs were induced in vitro,leptin with scalar doses was cocultured with BMDCs,IL-1β and IL-18 mRNA expression and protein secretion level were measured by q-RT-PCR and ELISA respectively.Caspase-1 activity or ROS synthesis were tested with FLICA kit or ROS detection assay kit on flow cytometry.IL-1β or IL-18 were detected after caspase-1 was inhibited by Ac-YVAD-cmk or NLRP3 was interfered by siRNA or ROS inhibitor DPI or KCL were added.Results: Leptin promoted secretion of IL-1β and IL-18.Leptin up-regulated NLRP3 and activted caspase-1 to secret proinflammtory cytokine,which K+ efflux took part in.Conclusion: Leptin promotes secretion of IL-1β and IL-18 by activating NLRP3 inflammasome,and K+ efflux takes part in this,which hints us that leptin may be an activator of NLRP3 inflammasome.