1.Discovery of selective HDAC6 inhibitors driven by artificial intelligence and molecular dynamics simulation approaches.
Xingang LIU ; Hao YANG ; Xinyu LIU ; Minjie MOU ; Jie LIU ; Wenying YAN ; Tianle NIU ; Ziyang ZHANG ; He SHI ; Xiangdong SU ; Xuedong LI ; Yang ZHANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(8):101338-101338
Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC50 = 5.41 nM) than that of tubastatin A (TubA) (IC50 = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC50 = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.
2.Monitoring results and analysis of key endemic disease prevention and control projects in Shanxi Province in 2021
Man HE ; Jianlyu YANG ; Qingzhen JIA ; Yongping WANG ; Zhenghui WANG ; Xiangdong ZHANG ; Fengfeng ZHANG
Chinese Journal of Endemiology 2024;43(8):643-646
Objective:To investigate the current situation of key endemic disease prevention and control in Shanxi Province, and provide a scientific basis for further strengthening the implementation of prevention and control measures.Methods:In 2021, monitoring of key endemic disease prevention and control projects in Shanxi Province was carried out in accordance with the current national monitoring plans for iodine deficiency disorders and water source high iodine areas, for endemic fluorosis, endemic arsenic poisoning, Kashin-Beck disease, and Keshan disease. The effect of prevention and control measures was evaluated in accordance with the "Evaluation Measures for Key Endemic Disease Control and Elimination (2019 Edition)". Patient management services and treatment subsidy projects were carried out in accordance with the "Management Service Standards for Endemic Disease Patients" and the "Management Measures for Treatment of Endemic Disease Patients".Results:All 117 counties (cities, districts, hereinafter referred to as counties) in Shanxi Province had reached the national elimination standards for iodine deficiency disorders, and the overall iodine nutrition of the population was generally suitable. However, the consumption rate of qualified iodine salt in 8 counties was ≤90%, and the iodine nutrition of pregnant women in 13 counties was insufficient. The water improvement rate in 295 villages in 12 counties across the province with high water iodine level was 80.68% (238/295), and the proportion of villages with qualified water iodine after water improvement was 38.31% (113/295). The prevention and control measures of 93.55% (58/62) of the counties in the province with endemic fluorosis caused through drinking water reached the national control standards. Totally 20 counties ravaged by coal-burning borne endemic fluorosis, 16 counties ravaged by drinking water borne endemic arsenicosis (high arsenic areas), 35 counties ravaged by Kashin-Beck disease, and 11 counties ravaged by Keshan disease met the national elimination standards. In 2021, 11 197 patients with endemic diseases were followed up and managed in Shanxi Province, and drug treatment programs were carried out on 3 413 patients with skeletal fluorosis, 2 088 patients with Kashin-Beck disease, and 10 patients with chronic Keshan disease.Conclusions:The overall prevention and control of key endemic diseases in Shanxi Province remains under control or elimination. However, the water improvement in some drinking water borne endemic fluorosis areas still needs to be further strengthened. Measures for water improvement and supply of non-iodized salt in water source high iodine areas still need to be coordinated and promoted. Key endemic disease patients in Shanxi Province have basically achieved standardized management.
3.Study on quality evaluation of Buddleja officinalis from different habitats based on HPLC fingerprint and content determination
Cuijie WEI ; Xiaoxia LIU ; Zhiwen DUAN ; Yongwei FENG ; Xiaozhou JIA ; Yueyi LIANG ; Xiangdong CHEN ; Dongmei SUN ; Zhenyu LI
International Journal of Traditional Chinese Medicine 2024;46(2):215-221
Objective:To establish UPLC fingerprint method and 2 contents determination methods of Buddleja officinalis; To provide a reference for improving the quality control standard and evaluation of Buddleja officinalis from different habitats.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddleja officinalis. The similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to compare the quality differences of Buddleja officinalis from different habitats. The contents of acteoside and linarin in Buddleja officinalis were determined.Results:There were 12 common peaks in UPLC fingerprints of Buddleja officinalis, six of which were identified as echinacoside, acteoside, cynaroside, isoacteoside, linarin, and apigenin. The fingerprint similarity of 17 batches of Buddleja officinalis was more than 0.9; Buddleja officinalis from different habitats were classified into 2 groups. Five differential markers were determined by OPLS-DA analysis. The order of significance was acteoside > peak 3 > echinacoside > isoacteoside > linarin. Edgeworthia chrysantha was identified by the method of fingerprint as counterfeit. The results of content determination showed that the content of Buddleja officinalis in Hubei and Sichuan was the high and stable.Conclusion:The method can effectively analyze the differences of Buddleja officinalis from different habitats, and provide reference for the quality control of Buddleja officinalis.
4.Clinical and translational mode of single-cell measurements:clinical artificial intelligent single-cell
Xiangdong WANG ; A.Powell CHARLES ; Qin MA ; Jia FAN
Chinese Journal of Clinical Medicine 2024;31(5):691-695
With rapid development and maturity of single-cell measurements,single-cell biology and pathology has become an emerging discipline to understand the disease.However,it is important to address concerns raised by clinicians as to how to apply single-cell measurements for clinical practice,translate the signals of single-cell systems biology into determination of clinical phenotype,and predict patient response to therapies.This paper proposes a new system coined as the clinical artificial intelligent single-cell(caiSC)with the dynamic generator of clinical single-cell informatics,artificial intelligent analyzers,molecular multimodal reference boxes,clinical inputs and outputs,and AI-based computerization.This system provides reliable and rapid information for impacting clinical diagnoses,monitoring,and prediction of the disease at the single-cell level.The caiSC represents an important step and milestone to translate the single-cell measurement into clinical application,assist clinicians'decision-making,and improve the quality of medical services.There is increasing evidence to support the possibility of the caiSC proposal,since the corresponding biotechnologies associated with caiSCs are rapidly developed.Therefore,we call the special attention and efforts from various scientists and clinicians on the caiSCs and believe that the appearance of the caiSCs can shed light on the future of clinical molecular medicine.
5.Analysis of risk factors for massive hemorrhage during cesarean section of pernicious placenta previa and establishment of risk prediction model
Yan MA ; Kai YANG ; Shanshan WANG ; Yihu MA ; Jia LIANG ; Junru ZHANG ; Xiangdong MA
Chongqing Medicine 2024;53(11):1650-1655
Objective To explore the influencing factors of massive hemorrhage during cesarean section of pernicious placenta previa,and establish a risk prediction model.Methods The clinical data of 340 pregnant women with pernicious placenta previa who underwent cesarean section for termination of pregnancy in this hospital from January 2017 to December 2021 were collected.They were divided into the common hemorrhage group (the amount of intraoperative blood loss<2000 mL,n=200) and massive hemorrhage group (the a-mount of intraoperative blood loss ≥2000 mL,n=140).The clinical characteristics of pregnant women,clini-cal data of this pregnancy,situation of the fetus,and imaging information were compared between the two groups.Combining the variables with a P value<0.05 in the univariate analysis and the possible influencing factors of massive hemorrhage during cesarean section in pregnant women with pernicious placenta previa in clinical practice,the binary multivariate logistic regression analysis was conducted,and a risk prediction model was established.Hosmer-Lemeshow goodness of fit test and receiver operating characteristic (ROC) curve were used to evaluate the fitting effect and discrimination of the model.Results The results of multivariate logistic regression analysis showed that the number of abortions,placental thickness,combining with placental implantation,number of previous cesarean sections and fetal gender were the independent influencing factors for massive hemorrhage (≥2000 mL) during cesarean section in pregnant women with pernicious placenta previa (P<0.05).The prediction model formula:P=Log (Y/1-Y),Y=0.396+1.371×(number of abor-tions=three times)+1.248×(number of abortions ≥ four times)-0.351×(placental thickness)+0.624× (combining with placental implantation)+0.974×(two or more previous cesarean sections)+0.638 × (female=0,male=1).The results of Hosmer-Lemeshow goodness of fit test showed that the prediction mod-el had good calibration ability (x2=77.825,P<0.001).The area under the ROC curve was 0.768 (95%CI:0.717-0.820),the specificity was 83.0%,the positive predictive value was 70.2%,and the negative predic-tive value was 73.5%.Conclusion The risk prediction model of massive hemorrhage during cesarean section in pregnant women with pernicious placenta previa has good performance.It is helpful to identify high-risk pregnant women in the prenatal evaluation,and provide a basis for formulating the blood transfusion plan in clinic,and prevention and treatment of adverse pregnancy outcomes.
6.Expert consensus on the diagnosis and treatment of chronic sinusitis in children.
Yong FU ; Jia LIU ; Jing LI ; Keqing ZHAO ; Qinglong GU ; Wei SONG ; Qi LI ; Yan JIANG ; Jing YE ; Xiangdong WANG ; Jiren DAI ; Hongtian WANG ; Yu XU ; Meiping LU ; Wenlong LIU ; Hongbing YAO ; Yong LI ; Huabin LI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(12):1091-1099
Objective:Pediatric chronic sinusitis (CRS) is a common disease within the field of otolaryngology-head and neck surgery. Due to the immaturity of sinus development and immune competence in children, its etiology and pathophysiology are complex, and its clinical features and outcomes differ significantly from those in adult patients. Currently, there are issues in the diagnosis and treatment of pediatric CRS, particularly in areas such as antibiotic use and surgical interventions, owing to a lack of sufficient attention. In recognition of this, the Chinese Rhinopathy Research Cooperation Group developed this expert consensus based on a systematic review of the latest literatures from both domestic and international sources, with reference to the latest evidence-based medical evidence worldwide, and in combination with their own clinical experience. The consensus covers various aspects including epidemiology, predisposing factors, pathophysiology, diagnosis and differential diagnosis, as well as treatment strategies such as medical therapy and surgical intervention. It aims to standardize the clinical diagnosis and treatment of pediatric CRS, improve clinical efficacy and patient satisfaction, reduce clinical expenditures, and decrease the occurrence of adverse reactions.
Humans
;
Sinusitis/therapy*
;
Chronic Disease
;
Child
;
Consensus
;
Anti-Bacterial Agents/therapeutic use*
7.Discussion on developing technical indicators for controlling the hazards of water-borne iodine excess in China
Xiangdong ZHANG ; Qingzhen JIA ; Yongping WANG
Chinese Journal of Endemiology 2023;42(10):847-851
The hazards of water-borne iodine excess is a relatively serious public health problem in China. The government has made great progress in prevention and controlling of the hazards of water-borne iodine excess through measures such as supplying non-iodized salt and implementing measures such as improving water quality to decrease iodine. However, there is a lack of corresponding evaluation criteria for measuring the implementation level and effectiveness of prevention and control measures, which urgently needs to be addressed. This article explores the technical indicators for establishing control standards for water source high iodine hazards in China through a review and analysis of relevant laws and regulations, normative documents, standards, and research progress in the field of high iodine prevention and control at home and abroad. It is recommended that administrative villages be used as units to evaluate the control status of water source high iodine hazards; after water improvement and iodine reduction, the iodine content of residents' drinking water should be ≤100 μg/L; meanwhile, the median urinary iodine for school-age children should be between 100 and < 300 μg/L, thyroid enlargement rate should be less than 5%.
8.Study on comprehensive quality evaluation of Sargentodoxae Caulis from different habitats
Weisheng LYU ; Cuijie WEI ; Zhenyu LI ; Hui LIANG ; Binbin SHEN ; Xiangdong CHEN ; Congyou DENG ; Xiaozhou JIA
International Journal of Traditional Chinese Medicine 2023;45(8):1004-1010
Objective:To comprehensively evaluated the quality of Sargentodoxae Caulis from different habitats with a combination of indexes and characteristic chromatogram method from Chinese Pharmcopoeia (Edition 2020). Methods:The contents of water content, total ash, ethanolic extract, sulfur dioxide residue, heavy metals and harmful elements, total phenols, chlorogenic acid, salidroside and characteristic chromatogram of 17 batches of Sargentodoxae Caulis were determined. The quality of Sargentodoxae Caulis was comprehensively evaluated by combining chemical pattern recognition method. Results:The water content, total ash content, extracts, and content determination of 17 batches of Sargentodoxae Caulis from different habitats complyed with the provisions of the Chinese Pharmcopoeia (Edition 2020). There were differences in the contents of extracts, chlorogenic acid, and salidroside, among which the content of Anhui origin was higher. A total of 8 common peaks were identified from the 17 batches samples. Conclusion:Comprehensive evaluation of multiple indicators can demonstrate the quality of Sargentodoxae Caulis more correctly, and shows that the quality of Sargentodoxae Caulis from different habitats is different. The quality of Sargentodoxae Caulis from Anhui is better than that from other habitats.
9.An epidemiological survey of thyroid disease in adults in different water iodine areas of Shanxi Province
Junmin GUO ; Qingping WANG ; Xiangdong ZHANG ; Fengfeng ZHANG ; Qingzhen JIA
Chinese Journal of Endemiology 2022;41(1):44-48
Objective:To investigate the prevalence of thyroid disease in adults in different water iodine areas and to explore the association between iodine and thyroid disease.Methods:In May of 2016, using cross-sectional survey, Gaoche Village and Maxi Village of Wenshui County were selected in Shanxi Province as a high-iodine area and a low-iodine area, respectively, Xiwenzhuang Village of Taiyuan City as an appropriate-iodine area. Questionnaire surveys, urinary iodine levels, thyroid ultrasound, determination of thyroid function and autoantibody were conducted for permanent residents aged 18 - 65.Results:A total of 898 people were investigated, including 288 in high-iodine area, 324 in low-iodine area and 286 in appropriate-iodine area. The medians urinary iodine were 417.8, 126.6 and 216.5 μg/L in high, low and appropriate-iodine areas, respectively, and the difference was statistically significant ( H = 288.61, P < 0.05). After age and sex standardization, the detection rates of hyperthyroidism in low, appropriate and high-iodine areas were 0.27%, 1.06% and 1.43%, respectively. The detection rates of sub-clinical hyperthyroidism were 0.57%, 0.31% and 0.30%, respectively. The detection rates of hypothyroidism were 1.45%, 1.15% and 1.85%, respectively. The detection rates of sub-clinical hypothyroidism were 19.34%, 28.50% and 32.76%, respectively. The detection rates of thyroid nodule were 20.51%, 20.17% and 33.78%, respectively. The positive rates of anti-thyroglobulin antibodies (TgAb) were 18.13%, 19.41% and 11.99%, respectively. The positive rates of thyroid peroxidase antibody (TPOAb) were 9.25%, 12.04% and 8.97%, respectively. The appropriate-iodine area was used as control, logistic regression analysis showed that only the detection rate of thyroid nodule in high-iodine area was significantly higher than that in appropriate-iodine area [odds ratio ( OR) = 0.488 5, 95% confidence interval ( CI) = 0.327 2 - 0.729 2 , P < 0.05]. Conclusion:In Shanxi Province, the detection rate of thyroid nodules is different in different areas of water iodine, and the detection rate of thyroid nodule in adults in high-iodine area is higher than that in other areas.
10.Experiences in use of kissing pancreatojejunostomy in 267 cases of pancreatoduodenectomy
Jia WU ; Xiangdong CHENG ; Yuhua ZHANG ; Yian DU ; Zhiyuan XU ; Litao YANG ; Fang HAN
Chinese Journal of General Surgery 2022;37(5):344-347
Objective:To investigate feasibility, efficiency and safety of kissing pancreatojejunostomy after pancreatoduodenectomy.Methods:From Jan 2006 to Sep 2020, the clinical data of 267 patients undergoing pancreatoduodenectomy and kissing pancreatojejunostomy were retrospectively analyzed.Results:Grade B postoperative pancreatic fistula (POPF) occurred in 6.37%, Grade C POPF in 2.25% of patients. There was no mortality within 30 days postoperatively as to pancreatic fistula, by cut-off of pancreatic duct diameter at 3mm, there was no significant difference between two subgroups (15/140 vs. 8/127, P=0.20). also, when grouped by texture of the pancreas, no there was significant difference (20/194 vs. 3/73, P=0.11). Conclusions:Kissing pancreatojejunostomy is feasible and easy to perform. It also does not increase the POPF rate when applied to the pancreatojejunostomy with thin pancreatic duct and soft texture.

Result Analysis
Print
Save
E-mail