1. A new strategy for evaluating antitumor activity in vitro with time-dimensional characteristics of RTCA technology
Fang-Tong LIU ; Shu-Yan XING ; Jia YANG ; Guo-Ying ZHANG ; Rong RONG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG ; Xiao-Yun LIU ; Dong-Xue YE ; Rong RONG ; Yong YANG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG ; Xiao-Yun LIU ; Dong-Xue YE ; Yong YANG
Chinese Pharmacological Bulletin 2024;40(3):592-598
Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1^1) used to calculate the EC50 value within this time dimension. The EC50 of baicalin, astragaloside, hesperidin and cisplatin on A549 cells was 52. 97 ±1.75 плпо! • L~1(16~48 h) , 62.88 ± 2.91 ijunol • L"1 (32.25 -48 h) , 78.84 ±0.33 плпо1 • L"1 (21.5 -29.75 h), 13.57 ±1.54 плпо1 • L_1(27.5 -48 h), respectively; the EC50 of baicalin, astragaloside, hesperidin and cisplatin on H1299 cells was 43. 71 ± 1. 26 |лто1 • L_1 ( 19. 5 -48 h), 47.23 ±1. 19 |лто1 • L_1(14 -48 h) , 39.45 ±0.24 плпо1 • L"1 (12.75 -46.25 h), 25.97 ±4.76 плпо1 • L"1 (10. 25 -48 h) , respectively. The results showed that the time window for the anti-tumor effect of the test solution/drug was different. Conclusions Based on RTCA technology, it is more accurate and reasonable to select EC50 data that exhibit better fitting, stable changes, and time-dimensional characteristics for the evaluation of anti-tumor activity. In addition, this method of distinguishing different effective time of antitumor drugs can provide a reference for the timing of clinical combination drugs, and this approach will also provide a reference for further related studies.
2.Circular RNAs Involved in The Development of Nasopharyngeal Carcinoma
Si-Cheng ZUO ; Dan WANG ; Yong-Zhen MO ; Yu-Hang LIU ; Jiao-Di CAI ; Can GUO ; Fang XIONG ; Guo-Qun CHEN
Progress in Biochemistry and Biophysics 2024;51(4):809-821
Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.
3.The effect of ultrasound-guided myofascial tube combined with knee joint posterior capsule space block on postoperative delirium in elderly patients undergoing total knee arthroplasty
Jia LIU ; Xiaoliang WANG ; Wenwen ZHANG ; Yajie XU ; Yong ZHANG ; Zhaojing FANG ; Lili ZHU
Journal of Chinese Physician 2024;26(3):354-359
Objective:To evaluate the effect of ultrasound-guided adductor canal combined with knee joint posterior capsule space block on the recovery period delirium in elderly patients undergoing total knee arthroplasty (TKA).Methods:A total of 68 elderly patients who underwent unilateral TKA at the Nanjing First Hospital from December 2021 to December 2022 were selected. They were randomly divided into a control group ( n=34) and an observation group ( n=34) using a random number table method. Both groups received general anesthesia, and the observation group received ultrasound-guided myofascial tube combined with knee joint posterior capsule space block before the surgery began. The incidence of delirium within 24 hours after surgery was mainly observed in two groups of patients. The surgical time, recovery time, intraoperative blood loss, infusion volume, total use of propofol and remifentanil were recorded; The resting and motor Visual Analogue Scale (VAS) scores of the patient were recorded at 4, 8, and 24 hours postoperatively. The patient′s serum tumor necrosis factor-α (TNF-α) and melatonin levels were measured on the day before surgery, the evening after surgery, and the first day after surgery. The subjective sleep quality score was recorded on the first day after surgery; The total dosage of sufentanil for patient-controlled intravenous analgesia (PCIA) within 24 hours after surgery, the effective number of compressions (P1) and actual number of compressions (P2) of PCIA, and the number of cases of additional oxycodone analgesia were recorded; The occurrence of respiratory depression, excessive sedation, nausea, and vomiting within 24 hours after surgery was recorded; The occurrence of complications of nerve block in the observation group was recorded. Results:The incidence of delirium during the recovery period in the observation group was lower than that in the control group ( P<0.05). The dosage of propofol and remifentanil in the observation group was lower than that in the control group (all P<0.05), and the awakening time was shorter than that in the control group ( P<0.05). The VAS scores at rest and exercise at 4, 8, and 24 hours after surgery in the observation group were lower than those in the control group (all P<0.05). Compared with the day before surgery, the observation group showed an increase in melatonin levels on the night after surgery ( P<0.05) and an increase in TNF-α levels on the first day after surgery ( P<0.05); The control group had a decrease in melatonin levels on the first day after surgery ( P<0.05), and an increase in TNF-α levels on the night and day after surgery (all P<0.05). The serum melatonin levels in the observation group were higher than those in the control group on the evening and first day after surgery (all P<0.05), and TNF-α levels were lower than those in the control group (all P<0.05). The subjective sleep quality score of the observation group showed that the total dosage of PCIA sufentanil, P1, P2, and the number of cases of additional oxycodone analgesia within 24 hours after surgery were lower than those of the control group (all P<0.05). The incidence of nausea in the control group (13 cases, 38.2%) was higher than that in the observation group (3 cases, 8.8%) ( P<0.05). Conclusions:In elderly patients undergoing unilateral TKA under general anesthesia, preoperative use of ultrasound-guided adductor tube combined with knee joint posterior capsule space block can effectively reduce the occurrence of postoperative delirium.
4.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
5.Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024)
Xiao CHEN ; Hao ZHANG ; Man WANG ; Guangchao WANG ; Jin CUI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Guohui LIU ; Zhongmin SHI ; Lili YANG ; Zhiwei WANG ; Guixin SUN ; Biao CHENG ; Ming CAI ; Haodong LIN ; Hongxing SHEN ; Hao SHEN ; Yunfei ZHANG ; Fuxin WEI ; Feng NIU ; Chao FANG ; Huiwen CHEN ; Shaojun SONG ; Yong WANG ; Jun LIN ; Yuhai MA ; Wei CHEN ; Nan CHEN ; Zhiyong HOU ; Xin WANG ; Aiyuan WANG ; Zhen GENG ; Kainan LI ; Dongliang WANG ; Fanfu FANG ; Jiacan SU
Chinese Journal of Trauma 2024;40(3):193-205
Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
6.The application value of spectral CT venography in the display and staging of deep venous thrombosis in the lower extremity
Shigeng WANG ; Yijun LIU ; Xin FANG ; Beibei LI ; Xu WANG ; Zhiming MA ; Xiaoyu TONG ; Yong FAN ; Wei WEI ; Anliang CHEN
Journal of Practical Radiology 2024;40(3):478-482
Objective To investigate the application value of spectral computed tomography venography(CTV)in the display and staging of deep venous thrombosis(DVT)in the lower extremity.Methods Eighty-two patients with CTV were selected and ran-domly divided into group A(42 patients)and group B(40 patients).Group A:tube voltage 120 kVp.Group B:gemstone spectral ima-ging(GSI)mode,reconstruction of 50 keV and iodine(water)maps.The CT and standard deviation(SD)values of the veins were measured,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated in 120 kVp images of group A and in 50 keV images of group B.Two observers scored the image quality of the 2 groups subjectively,and Kappa test was used to examine the con-sistency.Based on the duration from the occurrence of clinical symptoms,the DVTs were classified.The CT values and iodine con-centration(IC)of DVT were measured in the 120 kVp images of group A and in the iodine(water)maps of group B,respectively.The receiver operating characteristic(ROC)curve was drawn to compare the effectiveness of CT values and IC in diagnosing DVT staging.Results CT values,SNR,and CNR of veins in group B were higher than those in group A(P<0.05).The subjective scores of the two groups were consistent(Kappa=0.926-0.955,P<0.05).The score for the display of veins and thrombus clarity in group B was 5(4,5),which was better than the score of 4(3,4)in group A(P<0.05).The efficiency of IC in diagnosing DVT staging[area under the curve(AUC)=0.973]was better than that of CT values(AUC=0.891).Conclusion The spectral CTV can improve the contrast of lower extremity deep veins and the clarity of thrombus,and can provide more objective indicators for the diagnosis of thrombus staging,which is conducive to accurate clinical diagnosis and treatment.
7.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.
8.Analysis of risk factors for hemorrhage during CT-guided lung biopsy based on a random forest model
Yong LI ; Xiaohui ZHAO ; Fang LIU ; Wenge XING ; Fengjuan LI ; Jinhai SHI ; Jiaxin LIU ; Chengmin YANG
Chinese Journal of Blood Transfusion 2024;37(10):1110-1114,1121
Objective To systematically analyze and identify key risk factors for postoperative pulmonary hemorrhage u-sing a combination of the random forest(RF)model and traditional logistic regression analysis,so as to provide data support for clinical practice.Methods This study included patients who underwent needle biopsy of lung masses from January 2020 to December 2023 in the Department of Interventional Therapy,Cancer Hospital,Tianjin Medical University.There were 844 cases,including 387 males and 457 females,ranging in age from 39 to 82 years.Clinical data and puncture-related characteristics were collected,including tumor size,puncture depth,puncture angle,presence of emphysema,lesion loca-tion in the lung,body position during puncture,whether the puncture passed through the interlobar fissure,and the number of punctures.The RF model was used to rank the importance of all variables,identifying those with the highest predictive value.Subsequently,a multivariate logistic regression model was applied to the top-ranked important variables to further e-valuate their independent impact on postoperative pulmonary hemorrhage.Results The RF model results showed that tumor size and puncture depth had the highest importance in predicting the risk of postoperative pulmonary hemorrhage.Multivari-ate logistic regression analysis further confirmed that smaller tumor size(HR:0.980,95%CI:0.971-0.989,P<0.05)was significantly associated with a lower risk of hemorrhage,while greater puncture depth(HR:1.146,95%CI:1.063-1.235,P<0.05)was closely related to a higher risk of hemorrhage.Additionally,other factors such as puncture angle,age,lesion location in the lung and presence of emphysema showed some influence but did not reach statistical significance in the multi-variate analysis.Conclusion This study successfully identified tumor size and puncture depth as independent risk factors for postoperative pulmonary hemorrhage by combining the RF model with multivariate logistic regression analysis.The appli-cation of the RF model improved the accuracy of feature selection,allowing us to focus on the most contributory predictive variables.These findings provide important support for preoperative risk assessment,suggesting that clinicians should priori-tize these key factors in preoperative evaluations to develop safer and more effective surgical plans,thereby reducing the risk of postoperative hemorrhage and other complications.
9.Effects of emodin modulation of the HIF-1α/VEGF pathway on vascular endothelial cells damage in diabetic macroangiopathy rats
Qiu-Xiao ZHU ; Hui-Yao HAO ; Zi-Bo LIU ; Ming GAO ; Fang ZHANG ; Jing ZHOU ; Zhi-Hua HAO ; Li-Hui ZHANG ; Yong-Mei HAO
The Chinese Journal of Clinical Pharmacology 2024;40(6):859-863
Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)%,(6.28±0.20)%,(24.96±1.18)%,(12.36±0.49)%,(18.76±0.68)%and(4.59±0.26)%;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P<0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.
10.Pharmacokinetics of single-dose of Etripamil nasal spray in healthy adult Chinese subjects
Wei LIU ; Guo-Ying CAO ; Shu-Yan YU ; Yue-Wen XI ; Jing-Hui LUO ; Bo LIU ; Yu HE ; Tong-Yong FANG ; Xiao-Wen CHEN ; Yuan LI ; Jing ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1948-1952
Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65%from peak value at 25 min after dosing,and close to 80%within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)%.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

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