1.Outcomes of empirical versus precise lung segmentectomy guided by artificial intelligence: A retrospective cohort study
Jian CHEN ; Bicheng ZHAN ; Yong TANG ; Yongzhi LIU ; Genshui LI ; Jian LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(10):1422-1427
Objective To compare the clinical application of empirical thoracoscopic segmentectomy and precise segmentectomy planned by artificial intelligence software, and to provide some reference for clinical segmentectomy. Methods A retrospective analysis was performed on the patients who underwent thoracoscopic segmentectomy in our department from 2019 to 2022. The patients receiving empirical thoracoscopic segmentectomy from January 2019 to September 2021 were selected as a group A, and the patients receiving precise segmentectomy from October 2021 to December 2022 were selected as a group B. The number of preoperative Hookwire positioning needle, proportion of patients meeting oncology criteria, surgical time, intraoperative blood loss, postoperative chest drainage time, postoperative hospital stay, and number of patients converted to thoracotomy between the two groups were compared. Results A total of 322 patients were collected. There were 158 patients in the group A, including 56 males and 102 females with a mean age of 56.86±8.82 years, and 164 patients in the group B, including 55 males and 109 females with a mean age of 56.69±9.05 years. All patients successfully underwent thoracoscopic segmentectomy, and patients whose resection margin did not meet the oncology criteria were further treated with extended resection or even lobectomy. There was no perioperative death. The number of positioning needles used for segmentectomy in the group A was more than that in the group B [47 (29.7%) vs. 9 (5.5%), P<0.001]. There was no statistical difference in the number of positioning needles used for wedge resection between the two groups during the same period (P=0.572). In the group A, the nodule could not be found in the resection target segment in 3 patients, and the resection margin was insufficient in 10 patients. While in the group B, the nodule could not be found in 1 patient, and the resection margin was insufficient in 3 patients. There was a statistical difference between the two groups [13 (8.2%) vs. 4 (2.4%), P=0.020]. There was no statistical difference between the two groups in terms of surgical time, intraoperative blood loss, duration of postoperative thoracic drainage, postoperative hospital stay, or conversion to open chest surgery (P>0.05). Conclusion Preoperative surgical planning performed with the help of artificial intelligence software can effectively guide the completion of thoracoscopic anatomical segmentectomy. It can effectively ensure the resection margin of pulmonary nodules meeting the oncological requirements and significantly reduce the number of positioning needles of pulmonary nodules.
2.Advances in HIV-1 latency-regulating agents
Jiao-jiao DAI ; Xiang-yi JIANG ; Da FENG ; Hao LIN ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(4):840-852
At present, there is no cure for acquired immune deficiency syndrome (AIDS) due to HIV-1 latent reservoirs. Therefore, it urgently requires novel HIV-1 latency-regulating agents with high potency, low toxicity and favorable drug-like properties to achieve a functional cure for AIDS. Herein, we reviewed the advances in HIV-1 latency-regulating agents since 2019, including the drug discovery strategies, bioactivities, and mechanisms of these compounds. It is of great guiding significance in the development of latency-regulating agents with clinical value.
3.The underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry
Shuo WANG ; Bao-hu LI ; Shu-jing XU ; Yang ZHOU ; Jin-fei YANG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(7):1916-1931
Antiviral drug research and development is an important research direction in the current and future biomedical field. The research and development of antiviral drugs not only requires the application of new strategies and new technologies, but also requires the complementary advantages and close cooperation of project teams. Based on the latest progress in this field and the author's drug research practice, this paper summarizes the underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry.
4.Bioinformatics Analysis of Modified Lugen Formula in the Treatment of Influenza:Perspectives from the Virus-Host Interaction Network
Peng WU ; Yong JIANG ; Sha LI ; Wenyu WU ; Lichun JI ; Haidu HONG ; Gao ZHANG ; Huiting HUANG ; Xiaohong LIU ; Shaofeng ZHAN ; Yanni LAI
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):358-367
Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.
5.Simultaneous content determination of seventeen constituents in Yangxue Ruanjian Capsules by UPLC-MS/MS
Yong-Ming LIU ; Shu-Sen LIU ; Yi-Zhe XIONG ; Xiang WANG ; Yu-Yun WU ; Jin LIU ; Ling-Yun PAN ; Guo-Qing DU ; Hong-Sheng ZHAN
Chinese Traditional Patent Medicine 2024;46(2):353-358
AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.
6.Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase
Hui-nan JIA ; Rui-fang JIA ; Ji-wei ZHANG ; Yuan-min JIANG ; Chuan-feng LIU ; Ying ZHANG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(1):43-60
Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.
7.Research progress of anti-gout small molecules targeting the NLRP3 inflammasome
Zhen-qian WANG ; Zhi-jiao ZHANG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(3):543-553
Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.
8.Recent advances in drug screening methods of SARS-CoV-2 spike protein
Li-de HU ; Chuan-feng LIU ; Ping LI ; Guan-yu DONG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(2):298-312
The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells
9.A real-world study of clinicopathological characteristics and prognostic factors of gastrointes-tinal stromal tumor with initial surgical resection
Xiaona WANG ; Jingxin CAO ; Baogui WANG ; Hongjie ZHAN ; Yong LIU ; Xuewei DING ; Ning LIU ; Rupeng ZHANG ; Han LIANG
Chinese Journal of Digestive Surgery 2024;23(8):1080-1086
Objective:To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model. Results:(1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm 2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 <5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R 0 resection was in 814 cases and non-R 0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki-67 index, risk classification of NIH, and R 0 resection between the two groups ( χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P<0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection ( hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P<0.05). Conclusions:GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.
10.Data Mining of Traditional Chinese Medicine Syndrome Differentiation and Treatment Patterns for Dengue Fever
Ting WANG ; Cheng-Xin LIU ; Shao-Feng ZHAN ; Yong JIANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(9):2491-2499
Objective To investigate the patterns of traditional Chinese medicine(TCM)syndrome differentiation and treatment for dengue fever by using R language data visualization technology,so as to provide reference for TCM syndrome differentiation and treatment of dengue fever.Methods The related literature of dengue fever treated by Chinese medicine was retrieved from CNKI,Wanfang Data,and VIP.R-Studio software was used to conduct descriptive statistical analysis of the TCM syndromes,treatment methods,prescriptions and Chinese medicine in the literature of dengue fever treated by oral use of Chinese medicine.Based on Apriori algorithm,association rule mining and cluster analysis were carried out to explore the TCM syndrome and treatment patters of dengue fever.Results A total of 176 prescriptions for effective cases were extracted,and the included literature involved 29 syndromes,73 TCM treatment methods,56 classical prescriptions and 35 self-formulated prescriptions,and 179 Chinese medicinals.The syndrome of comorbidity of defense phase and qi phase and the syndrome of blazing of both qi phase and nutrient phase were the high-frequency syndromes of dengue fever treated by oral use of Chinese medicine.The high-frequency treatment methods covered heat-clearing therapy,toxin-removing therapy,blood-cooling therapy and dampness-resolving therapy.Qingwen Baidu Decoction was the most frequently-used prescription.Glycyrrhizae Radix et Rhizoma,Forsythiae Fructus,Scutellariae Radix,Gypsum Fibrosum,and Lonicerae Japonicae Flos were the frequently-used Chinese medinals.There were three drug combinations containing Paeoniae Radix Rubra,Moutan Cortex,and Rehmanniae Radix,and their correlation of association rules was the highest.Bubali Cornu,Moutan Cortex,Paeoniae Radix Rubra,Rehmanniae Radix,Lonicerae Japonicae Flos,Forsythiae Fructus,Gypsum Fibrosum,Scutellariae Radix,Anemarrhenae Rhizoma,and Glycyrrhizae Radix et Rhizoma were the core Chinese medicinals for the treatment of dengue fever.Conclusion The TCM syndromes of dengue fever are predominated by the syndrome of comorbidity of defense phase and qi phase and the syndrome of blazing of both qi phase and nutrient phase.The treatment of dengue fever with TCM is based on the principle of clearing heat toxin from the qi phase,cooling the nutrient-blood excess heat,resolving pathogenic dampness,and nourishing qi and yin.The treatment focuses on clearing qi phase and blood phase,and the application of removing stasis in febrile diseases should be stressed,thus to block the progression of the disease in time.

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