1.CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury.
Yong CHEN ; Xue YUAN ; Wei YAN ; Yurong ZOU ; Haoche WEI ; Yuhan WEI ; Minghai TANG ; Yulian CHEN ; Ziyan MA ; Tao YANG ; Kongjun LIU ; Baojian XIONG ; Xiuying HU ; Jianhong YANG ; Lijuan CHEN
Acta Pharmaceutica Sinica B 2025;15(7):3708-3724
Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.
2.Rifampicin and isoniazid resistance among pulmonary tuberculosis patients in Luohu District from 2012 to 2022
TANG Xiaofen ; QIN Daoxin ; JIN Fengxia ; TIAN Yuan ; ZOU Yongxia ; SHEN Yurong ; LIU Yao ; XIE Xiuchai
Journal of Preventive Medicine 2024;36(6):536-539
Objective:
To investigate the resistance to rifampicin and isoniazid and the changing trends among patients with pulmonary tuberculosis in Luohu District, Shenzhen City, Guangdong Province from 2012 to 2022, so as to provide insights into improving drug-resistant pulmonary tuberculosis control and prevention strategies.
Methods:
Basic information, treatment classification and drug resistance data of patients with pulmonary tuberculosis and positive pathogenic detection in Luohu District from 2012 to 2022 were collected through the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, and resistance rates of rifampicin and isoniazid and the changing trends were analyzed.
Results:
A total of 2 126 patients with pulmonary tuberculosis were collected and had a median age of 34 (interquartile range, 25) years, including 1 334 males (62.75%) and 792 females (37.25%). There were 302 patients with drug-resistance in Luohu District from 2012 to 2022, with a resistance rate of 14.21%. Among them, 60 patients were monoresistant to rifampicin (2.82%), 113 patients were monoresistant to isoniazid (5.32%), and 129 patients were multidrug resistant (6.07%). The rate of rifampicin monoresistance showed a downward trend from 2012 to 2022, while the rate of multidrug resistance showed an upward trend (both P<0.05). There was no significant tendency in the rate of isoniazid monoresistance (P>0.05). The rate of multidrug resistance among patients without Shenzhen residence was higher than that among patients with Shenzhen residence; the rates of rifampicin resistance and multidrug resistance among retreated patients were higher than those among treatment-naïve patients (all P<0.05).
Conclusions
The rate of rifampicin monoresistance appeared a downward trend and the rate of multidrug resistance appeared an upward trend among patients with pulmonary tuberculosis in Luohu District from 2012 to 2022. Attention should be given to non-Shenzhen residence and retreated patients.
3.Study on the biomarker of circular RNA in peripheral blood of Uygur patients with type 2 diabetes mellitus
Yurong ZHU ; Tao BA ; Jiehong KANG ; Yuan SUN ; Xiangyun CHANG
Chinese Journal of Diabetes 2024;32(1):6-10
Objective To explore the potential circular RNA(circRNA)biomarker of Uygur type 2 diabetes mellitus(T2DM).Methods A total of 120 T2DM patients and 120 subjects with normal glucose tolerance were recruited from the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Shihezi University and Shihezi community from October 2020 to August 2021,and divided into four groups:60 Uygur T2DM patients(Uygur T2DM group),60 Uygur subjects with normal glucose tolerance(Uygur NC group),60 Han T2DM patients(Han T2DM group)and 60 Han subjects with normal glucose tolerance(Han NC group).Hsa_circRNA_0042817,hsa_circRNA_0006532 and hsa_circRNA_0004131 were selected as candidate circRNA,and the expression in peripheral blood were detected by RT-qPCR.Logistic regression was used to analyze the influencing factors for Uygur T2DM,and the receiver operating characteristic(ROC)curve was used to evaluate the biomarker value of circRNA in Uygur T2DM.Results The expressions of hsa_circRNA_0042817,hsa_circRNA_0006532 and hsa_circRNA_0004131 were higher in Uygur T2DM group than in Uygur NC group(P<0.05).The expression of hsa_circRNA_0042817 was higher in Uygur T2DM group than in Han T2DM group(P<0.05).Logistic regression analysis showed that hsa_circRNA_0042817 was an influencing factor for T2DM in Uygur population[OR(95%CI)3.420(1.567~7.465)].ROC curve analysis showed that the area under the curve was the largest(0.798)in hsa_circRNA_0042817.Conclusion There were up-regulated circRNA in peripheral blood in Uygur T2DM patients,and hsa_circRNA_0042817 may be a biomarker for T2DM in Uygur patients.
4.Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer
Die SANG ; Shanmin FAN ; Shiyu LI ; Jintao ZHANG ; Hengmin WANG ; Xiaohui ZHAO ; Lijun ZHENG ; Ping LIANG ; Guangbiao XI ; Longmei ZHAO ; Yurong ZHANG ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):256-262
Objective:To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies.Methods:In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT.Results:In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant ( P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively ( OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions:In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.
5.A case of successful treatment of an extremely preterm infant born at 21 weeks and 4 days of gestation
Haifeng ZONG ; Bingchun LIN ; Yingsui HUANG ; Shan JIANG ; Yurong YUAN ; Xiaoyun XIONG ; Zhifeng HUANG ; Chuanzhong YANG
Chinese Journal of Perinatal Medicine 2024;27(10):860-864
This case report described the sucussful treatment of a male infant born at 21 weeks and 4 days through assisted reproductive technology. After prenatal consultation and with the strong desire of the parents, active resuscitation and treatment were performed. The infant received 52 days of mechanical ventilation and was extubated to non-invasive ventilation at a corrected gestational age of 28 weeks and 6 days. During hospitalization, no vasoactive drugs were used, and necrotizing enterocolitis did not occur. The gastric tube was removed at a corrected gestational age of 37 weeks and 4 days. At a corrected gestational age of 40 weeks, cranial MRI showed no abnormalities. The infant was discharged at a corrected gestational age of 42 weeks after 143 days of treatment, without the need for any respiratory support. Follow-up until a corrected age of 6 months showed good growth and development.
6.Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer
Die SANG ; Shanmin FAN ; Shiyu LI ; Jintao ZHANG ; Hengmin WANG ; Xiaohui ZHAO ; Lijun ZHENG ; Ping LIANG ; Guangbiao XI ; Longmei ZHAO ; Yurong ZHANG ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):256-262
Objective:To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies.Methods:In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT.Results:In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant ( P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively ( OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions:In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.
7.Application value of deep learning reconstruction algorithm in CT imaging of abdominal phantoms
Yurong ZHANG ; Qianqian YUAN ; Jianbo GAO ; Jie LIU
Chinese Journal of Radiological Medicine and Protection 2023;43(8):645-652
Objective:To explore the value of the deep learning image reconstruction (DLIR) algorithm in improving the CT image quality of abdominal phantoms under different radiation doses by comparing the DLIR algorithm with the conventional Adaptive Statistical Iterative Reconstruction-V (ASIR-V) technique.Methods:Two groups with tube voltages of 100 kV and 120 kV (also referred to as the 100 kV and 120 kV groups, respectively) were involved. Each group was further divided into six subgroups based on different volumetric CT dose indices (CTDI vol: 2, 4, 6, 8, 10 and 15 mGy). Subsequently, CT images based on the filtered back projection (FBP) algorithm were obtained and were then reconstructed using the ASIR-V algorithm with different weights (ASIR-V 50%, 80%, and 100%) and the DLIR algorithm with different levels (DLIR-L, M, and -H). As a result, 84 groups of images were obtained in total. Afterward, this study compared and analyzed the variations in CT values, noise, signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), and subjective scores of various parts in various CTDI vol subgroups under different reconstruction conditions. In addition, the subjective scores of the image quality were compared using the Kruskal-Wallis H test, while objective indices and radiation doses were compared through the univariate analysis of variance (ANOVA) and the paired t test. Results:Under the same tube voltage, there were statistically significant differences in the noise, SNRs, and CNRs of various parts in various CTDI vol subgroups under different reconstruction conditions ( F = 415.39, 315.30, P < 0.001), while there was no statistically significant difference in the noise, SNRs, and CNRs of images constructed using ASIR-V 50% and DLIR-L ( P > 0.05). Under different tube voltages, the subjective scores of both groups show statistically significant differences (100 kV group: H = 13.47, P = 0.036; 120 kV group: H = 12.99, P = 0.043). Moreover, two physicians offered consistent subjective scores, with Kappa values > 0.70. Among these images, DLIR-H images showed the highest subjective scores, followed by DLIR-M and ASIR-V 50% images, which had roughly consistent subjective scores. Moreover, the subjective scores of the 100 kV group were slightly higher than those of the 120 kV group. With the ASIR-V 50% images of the subgroup with a CTDI vol of 15 mGy as references, the DLIR-L, -M, and -H reduced radiation doses by more than 30%, 70% and 85%, respectively on the premise that diagnostic requirements were met. Conclusions:The DLIR algorithm can not only significantly reduce the image noise and improve the image quality, but also effectively decrease the radiation doses on the premise of meeting the diagnostic requirements. It is recommended that 100 kV tube voltage combined with a medium- or high-level DLIR algorithm should be applied to low-dose abdominal CT scans in clinical applications.
8.Analysis of urine Alzheimer-associated neuronal thread protein level and related factors of middle-aged and elderly people in Mianyang
Yurong ZHANG ; Kun FANG ; Renfei ZHANG ; Fang WANG ; Yang LIU ; Ping YANG ; Yan WU ; Lei LI ; Yuanyu ZHAO ; Zhilong CAI ; Jia YANG ; Dan YUAN
Sichuan Mental Health 2023;36(1):53-58
ObjectiveTo investigate the Alzheimer-associated neurofilament protein (AD7c-NTP) in urine of middle-aged and elderly people and its correlation between common metabolites. MethodsA total of 1 150 middle-aged and elderly people who did their physical exmanination in the health examination center of the Sichuan Science City Hospital and the Third Hopital of Mianyang were recruited from March 2017 to March 2020. The level of urine AD7c-NTP were measured by enzyme-linked immunosorbent assay (ELISA), and common metabolites in blood were measured by biochemical analyzer. Based on urine AD7c-NTP level ≤1.5 ng/mL, the objects was divided into normal group (n=956) and elevated group (n=194). Thier demographic data and blood biochemical indicators were collected. ResultsThe urine AD7c-NTP level in middle-aged and elderly people was 0.60(0.30~1.20) ng/mL. The urine AD7c-NTP level was higher in women than that in men [1.04(0.40~1.30) ng/mL vs. 0.84(0.30~1.00) ng/mL, Z=4.202, P˂0.01]. And the urine AD7c-NTP level was lower in the normal group than that in the elevated group [0.50(0.30~0.90) ng/mL vs. 2.10(1.70~2.10) ng/mL, Z=22.035, P˂0.01]. The results of the univariate comparison showed that, the differences between the two groups in age (Z=6.545), fasting glucose (Z=3.506), blood uric acid (Z=2.574), urea nitrogen (Z=2.891), creatinine (Z=2.243), total bilirubin (Z=3.936), glutathione (Z=0.969), total cholesterol (t=3.956) and low density lipoprotein (Z=-5.678) were were statistically significant (P˂0.05 or 0.01). Spearman correlation analysis showed that, the urine AD7c-NTP level was positively correlated with age and the levels of urea nitrogen, glucose, total cholesterol and low density lipoprotein (r=0.177, 0.178, 0.171, 0.109, 0.149, P˂0.01), and negatively correlated with the level of total bilirubin (r=-0.172, P˂0.01). Conclusionthe urine AD7c-NTP level in middle-aged and elderly females was signifitcantly higher than in middle-aged and elderly males.The urine AD7c-NTP level of middle-aged and elderly people was positively correlated with age, urea nitrogen, glucose, total cholesterol and low density lipoprotein, and negatively correlated with total bilirubin.
9.Effect of online and offline collaborative and integrated mode on voluntary blood donation: Internet + blood donation souvenir
Li YANG ; Jian CHEN ; Yurong YUAN ; Li ZHANG ; Wei LU ; Yi GUO ; Weihua ZHANG
Chinese Journal of Blood Transfusion 2023;36(8):735-737
【Objective】 To explore the effect of online and offline collaborative and integrated mode (Internet + blood donation souvenirs), and develop diversified scientific ways of caring for voluntary blood donors in combination with the potential expectation of the target population, ao as to recruit and retain more blood donors. 【Methods】 A total of 4 000 blood donors from Yichang Central Blood Station from January 1 to June 30, 2022 were selected, and they could collect souvenirs from online and offline. The intelligent platform V9.5 of modern blood station management information system of Qiao Technology was used to classify the data of online and offline souvenir distribution, and digital intelligent comparison and analysis on age, occupation, education, type (first-time blood donors or repeat blood donors), region (main urban districts of Yichang and other counties and suburban districts) and gender were carried out. 【Results】 A total of 1 400 blood donors chose online souvenirs, who were mainly under 25 years old, students, female, college education or above, urban areas and regular donors; 2 600 chose offline souvenirs, who were mainly over 25 years old, male, junior college degree or below, occupations other than students (medical workers, educators, etc.), counties and suburban districts, and first-time blood donors. The collaborative and integrated mode of the two distribution methods were complementary and had a good incentive effect on blood donor recruitment. 【Conclusion】 The online and offline collaborative and integrated mode demonstrates a good effect and meets the needs of different population. Digital intelligence system is helpful to develop diversified and scientific ways of caring for voluntary blood donors, recruit and retain more blood donors, achieve high-quality development of blood collection and supply, therefore guarantee the increasing demand for clinical blood use.
10.Recurrent neural network prediction on clinical usage of red blood cells
Fangyan WANG ; Yurong YUAN ; Min ZHANG ; Kun LI ; Wei LU
Chinese Journal of Blood Transfusion 2023;36(5):455-458
【Objective】 To explore the prediction of clinical red blood cells (RBCs) consumption under major public health emergencies, so as to provide scientific basis for blood collection and blood inventory management. 【Methods】 The clinical consumption of different types of RBCs in Yichang from 2001 to 2017 was analyzed and modeled using the recurrent neural network (RNN) model, and the clinical RBCs consumption between January 2019 and December 2021(36 months) were scientifically predicted. 【Results】 The RNN model showed good prediction performance. The root mean square errors (RMSE) of RNN prediction values of A, B, O, AB type of RBCs were 156.7, 133.4, 204.2 and 51.3, respectively, with the average relative errors (MRE) at 6.4%, 6.6%, 8.5% and 7.1%, respectively. The model predicted the changing trend of RBCs consumption during the first round of COVID-19 outbreak (January to June, 2020) and forecasted the lowest level of consumption in February 2020 and a subsequent recovery in growth. The prediction of RBCs consumption during the second round of COVID-19 pandemic (January to June, 2021) was of high accuracy. For example, the relative errors of RNN models for A type RBCs consumption were 5.2% in Feb 2021 (the lowest level, 1 621.5 U) and 2.5% in May 2021 (the highest level, 2 397.0 U). 【Conclusion】 The artificial intelligence RNN model can predict clinical RBCs consumption well under major public health emergencies.


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