1.Research progress on carrier-free and carrier-supported supramolecular nanosystems of traditional Chinese medicine anti-tumor star molecules
Zi-ye ZANG ; Yao-zhi ZHANG ; Yi-hang ZHAO ; Xin-ru TAN ; Ji-chang WEI ; An-qi XU ; Hong-fei DUAN ; Hong-yan ZHANG ; Peng-long WANG ; Xue-mei HUANG ; Hai-min LEI
Acta Pharmaceutica Sinica 2024;59(4):908-917
Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.
2.Quality standard for Zhujieshen Formula Granules based on standard decoction
Chen-Hui YE ; Hai-Ming TANG ; Cheng-Fu YUAN ; Jia-Long GUO ; Ji-Hong ZHANG ; Ding YUAN ; Yu-Min HE
Chinese Traditional Patent Medicine 2024;46(9):2863-2869
AIM To establish the quality standard of the zhujieshen Formula Granules based on standard decoction.METHODS The contents and transfer rates of ginsenoside Ro and chikusetsu saponin Ⅳa in standard decoction and formula granules were determined by HPLC,after which the transfer rates were calculated.The HPLC characteristic chromatograms of standard decoctions were established,after which cluster analysis and principal component analysis were adopted.Then the HPLC characteristic chromatograms of formula granules were established.RESULTS Nine common peaks were found in the HPLC characteristic chromatograms of seventeen batches of standard decoctions with the similarities of more than 0.9(except for S6,S12),which were clustered into two categories,and the accumulative variance contribution rate of three principal components reached 86.7%.The contents of ginsenoside Ro in three batches of formula granules were 83.1-88.6 mg/g,and the transfer rates were 53.1%-55.5%.The contents of chikusetsusaponin Ⅳa were 14.8-15.0 mg/g,and the transfer rates were 47.4%-48.1%.Nine common peaks were found in the HPLC characteristic chromatograms of three batches of formula granules with the similarities of 0.998,0.998 and 0.999,respectively.CONCLUSION This reasonable and reliable method can comprehensively evaluate the quality of Zhujieshen Formula Granules,and provide a reference for the quality control.
3.Clinical study of overlapping Wallstent stent implantation in large or giant extracranial internal carotid artery aneurysms
Qi TIAN ; Shuailong SHI ; Shuhai LONG ; Ji MA ; Ye WANG ; Xiao LI ; Renying MIAO ; Yan SONG ; Tengfei LI
Chinese Journal of Neuromedicine 2024;23(11):1086-1093
Objective:To assess the efficacy and safety of overlapping braided carotid artery stent (Wallstent) implantation in large extracranial internal carotid artery aneurysms (15 mm≤diameter<25 mm) and giant ones (diameter≥25 mm).Methods:A retrospective study was performed; the clinical data of 23 patients with large or giant extracranial internal carotid artery aneurysms accepted overlapping Wallstent stent implantation in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from August 2015 to June 2023 were collected. Immediately after implantation, DSA was used to evaluate the retention of contrast agent within the aneurysms and high-resolution C-arm CT (HR-CBCT) was used to detect the apposition between the two stents and between the stents and inner wall of the blood vessel. Perioperative complications were recorded. Clinical follow-up was performed bi-monthly via outpatient visits or telephone, and modified Rankin scale (mRS) was used to assess the prognoses (mRS scores of 0-2 as good prognosis) at the last follow-up; aneurysm occlusion was evaluated in a 6-month follow-up by DSA and in-stent restenosis in a final imaging follow-up by DSA or CTA according to the OKM grading. Results:Twenty-two patients had successful overlapping implantation of 2 Wallstent stents; blood flow was restricted in one patient due to carotid artery dissection at the distal end of the aneurysm during stent implantation and restored after a Neuroform EZ stent and 2 Wallstent stent implantation from the distal-proximal lesion; technical success rate of 95.7% (22/23) was obtained. DSA immediately after implantation showed obvious contrast medium retention in all aneurysms. HR-CBCT indicated good stent apposition in 21 patients and mild incomplete stent apposition in 2. Clinical follow-up was finished in 23 patients, ranged 6-31 months (mean 11.5±6.3 months); all patients had good prognosis at the last follow-up. Imaging follow-up, including at least once DSA, was conducted for all patients, with intervals ranging from 6 to 15 months (mean 10.4±3.4 months); DSA 6 months after implantation showed complete aneurysm occlusion in 19 patients (OKM grading D) and a bit of residual contrast in 4 patients (OKM grading C); final imaging follow-up (DSA in 2 and CTA in 21) revealed in-stent stenosis in 2 patients (stenosis rates of 51% and 87%) with obvious improved stenosis after balloon angioplasty and patent stents in 21 patients without evidence of aneurysm opacification.Conclusion:Overlapping braided carotid artery stent (Wallstent) implantation is an effective and safe approach for managing large or giant extracranial carotid artery aneurysms.
4.Effect of Diurnal Temperature Range on the Number of Residents Hospitalized Due to Stroke in Lanzhou.
Run-Ping ZHANG ; Wan-Cheng ZHANG ; Jiang-Long LING ; Ji-Yuan DONG ; Li ZHANG ; Ye RUAN
Acta Academiae Medicinae Sinicae 2023;45(6):934-939
Objective To analyze the relationship between diurnal temperature range (DTR) and the hospitalization of stroke in Lanzhou,so as to provide a scientific basis for probing into the mechanism of temperature changes in inducing stroke and formulating comprehensive prevention and control measures for stroke by relevant departments.Methods The information of the patients hospitalized due to stroke in Lanzhou during January 2014 to December 2019 and the air pollutants (PM10,SO2,and NO2) and meteorological data in the same period were collected for statistical analysis.Spearman rank correlation analysis was performed to analyze the correlations between air pollutants and meteorological factors.The distributed lag nonlinear model was adopted to fit the relationship between DTR and the number of stroke inpatients,and three-dimensional diagrams and the correlation diagrams of DTR against stroke risk were established.The stratified analysis was performed according to gender and age (< 65 years and ≥65 years).Results From 2014 to 2019,a total of 92 812 stroke patients were hospitalized in Lanzhou,with a male-to-female ratio of 1.35:1.There was a nonlinear relationship between DTR and the number of stroke inpatients in Lanzhou,which presented a lag effect.The low DTR at 4.5 ℃ had the largest RR value of 1.25 (95%CI=1.16-1.35) for stroke inpatients at a cumulative lag of 18 d.The effect of high DTR (18.5 ℃) on the hospitalization of stroke patients peaked at a cumulative lag of 21 d,with an RR value of 1.09 (95%CI=1.01-1.18).The stratified analysis results suggested that low levels of DTR had greater effects on the hospitalization of male stroke patients and stroke patients <65 years.Conclusions Short-term exposure to different levels of DTR had an impact on the number of stroke inpatients,and low levels of DTR had a slightly greater impact on stroke inpatients than high levels of DTR.Importance should be attached to the protection of males and people aged <65 years at low levels of DTR.
Humans
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Male
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Female
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Temperature
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Stroke
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Cold Temperature
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Hot Temperature
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Air Pollutants
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China/epidemiology*
5.The impact of the COVID-19 pandemic on erectile function in Chinese CP/CPPS patients.
Wei-Jie SONG ; Ji-Wei HUANG ; Yuan LIU ; Wei DING ; Zhi LONG ; Le-Ye HE
Asian Journal of Andrology 2023;25(6):680-686
This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on erectile function in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). A retrospective study was conducted on 657 CP/CPPS patients who visited The Third Xiangya Hospital of Central South University (Changsha, China) from November 2018 to November 2022. Patients were divided into two groups based on the timeline before and after the COVID-19 outbreak in China. The severity of CP/CPPS, penile erection status, anxiety, and depression was evaluated using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Index of Erectile Function-5 (IIEF-5), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. Compared with patients before the COVID-19 outbreak, more CP/CPPS patients developed severe erectile dysfunction (ED) due to depression and anxiety caused by the pandemic. After developing moderate-to-severe ED, mild and moderate-to-severe CP/CPPS patients exhibited more apparent symptoms of anxiety and depression ( P < 0.001 and P = 0.001, respectively), forming a vicious cycle. The COVID-19 pandemic has adversely affected the psychological status of CP/CPPS patients, exacerbating their clinical symptoms and complicating ED. The exacerbation of clinical symptoms further worsens the anxiety and depression status of patients, forming a vicious cycle. During the COVID-19 pandemic, paying more attention to the mental health of CP/CPPS patients, strengthening psychological interventions, and achieving better treatment outcomes are necessary.
Male
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Humans
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Erectile Dysfunction/etiology*
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Pandemics
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Penile Erection
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Prostatitis/complications*
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Retrospective Studies
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East Asian People
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COVID-19/complications*
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Chronic Disease
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Pelvic Pain/complications*
6.Neuroform EZ and Enterprise 2 stents in patients with symptomatic intracranial atherosclerotic stenosis: a comparative study
Shuhai LONG ; Sun YU ; Chengcheng SHI ; Shuailong SHI ; Ji MA ; Jie YANG ; Ye WANG ; Xinwei HAN ; Tengfei LI
Chinese Journal of Neuromedicine 2023;22(1):27-36
Objective:To explore the stent apposition and safety of Neuroform EZ and Enterprise 2 stents in treatment of symptomatic intracranial atherosclerotic stenosis (sICAS), and their influencing factors for in-stent restenosis.Methods:A total of 143 sICAS patients treated by Enterprise 2 stents (implanted 143 Enterprise 2 stents, E2 group) and 202 patients treated by Neuroform EZ stents (implanted 202 Neuroform EZ stents, EZ group) were selected from Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from January 2017 to January 2022. Stent apposition was evaluated based on reconstructive images of high-resolution flat detector CT. The complications 30 d after surgery and during 6-24 months of follow-up were recorded. Based on DSA or CTA 6 months after surgery, the patency of the two stents was evaluated. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent risk factors for in-stent restenosis.Results:(1) Forty-nine patients had incomplete stent apposition (ISA) after stent release: 24 patients with ISA in E2 group (16.8%, 24/143; 15 of type I and 9 of type II) and 25 with ISA in the EZ group (12.4%, 25/202, 11 of type I and 14 of type II) were found, without statistical difference ( χ 2=1.334, P=0.248); however, ISA incidence in the EZ group (19.0% and 10.3%) was significantly lower than that in the E2 group (41.4% and 25.6%) when the diameter ratio of anterior and posterior vessels of the stenosis lesions≥1.30 or the angle of stent≥75° ( χ 2=4.228, P=0.040; χ 2=4.531, P=0.033). (2) Within 30 d of stenting, 17 patients developed neurological dysfunction-related complications: 8 patients in EZ group and 9 in E2 group were noted, without significant difference ( P=0.324). Clinical follow-up was obtained in 317 patients, and 20 patients developed long-term stroke associated with responsible lesion vessels: 12 patients in EZ group and 8 in E2 group were noted, without significant difference ( P=0.995). (3) Totally, 298 patients received imaging follow-up 6 months after surgery, and 65 patients developed in-stent restenosis: 36 patients in EZ group and 29 in E2 group were noted, without significant difference ( χ 2=0.309, P=0.578). Multivariate Logistic regression analysis showed that diabetes ( OR=2.714, 95% CI: 1.437-5.126, P=0.002), stent apposition ( OR=3.435, 95% CI: 1.223-9.652, P=0.019), lesion stenosis length ( OR=1.176, 95% CI: 1.065-1.300, P=0.001) and immediate postoperative residual stenosis ( OR=1.038, 95% CI: 1.004-1.074, P=0.029) were independent influencing factors for in-stent restenosis. Conclusions:Enterprise 2 and Neuroform EZ stents have high stent apposition and safety in sICAS treatment, but in cases with large diameter ratio of the anterior and posterior vessels of the stenosis lesions (diameter ratio≥1.30) or large angle of the stent (≥75°), Neuroform EZ stent has better stent apposition. Patients with diabetes, ISA, long lesion stenosis or high residual stenosis may trend to have in-stent restenosis.
7.Research progress of ATR kinase-targeted inhibitors in the cancer therapy
Ying-hui YUAN ; Ji-long DUAN ; Zi HUI ; Tian XIE ; Xiang-yang YE
Acta Pharmaceutica Sinica 2022;57(3):593-604
Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.
8.Npac Is A Co-factor of Histone H3K36me3 and Regulates Transcriptional Elongation in Mouse Embryonic Stem Cells
Yu SUE ; Li JIA ; Ji GUANXU ; Ng Long ZHEN ; Siew JIAMIN ; Lo Ning WAN ; Ye YING ; Chew Yuan YUAN ; Long Chau YUN ; Zhang WENSHENG ; Guccione ERNESTO ; Loh Han YUIN ; Jiang ZHI-HONG ; Yang HENRY ; Wu QIANG
Genomics, Proteomics & Bioinformatics 2022;20(1):110-128
Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylation(H3K36me3),is required to maintain mouse ESC(mESC)pluripotency since knockdown of Npac causes mESC differentiation.Depletion of Npac in mouse embryonic fibroblasts(MEFs)inhibits reprogramming efficiency.Furthermore,our chromatin immunoprecipitation followed by sequencing(ChIP-seq)results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs.Interestingly,we find that Npac interacts with positive transcription elongation factor b(p-TEFb),Ser2-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser2P),and Ser5-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser5P).Furthermore,depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rifl.Taken together,we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interact-ing with RNA Pol Ⅱ Ser2P and Ser5P.
9.L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction
Hai Yan ZHAO ; Hui Ying LI ; Jian JIN ; Ji Zhe JIN ; Long Ye ZHANG ; Mei Ying XUAN ; Xue Mei JIN ; Yu Ji JIANG ; Hai Lan ZHENG ; Ying Shun JIN ; Yong Jie JIN ; Bum Soon CHOI ; Chul Woo YANG ; Shang Guo PIAO ; Can LI
The Korean Journal of Internal Medicine 2021;36(Suppl 1):S180-S195
Background/Aims:
Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro.
Methods:
Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC.
Results:
LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells.
Conclusions
LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.
10.Establishment and clinical application value of an automatic diagnosis platform for rectal cancer T-staging based on a deep neural network.
Qing-Yao WU ; Shang-Long LIU ; Pin SUN ; Ying LI ; Guang-Wei LIU ; Shi-Song LIU ; Ji-Lin HU ; Tian-Ye NIU ; Yun LU
Chinese Medical Journal 2021;134(7):821-828
BACKGROUND:
Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network.
METHODS:
A total of 183 rectal cancer patients' data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve.
RESULTS:
An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00.
CONCLUSION:
Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging.
TRIAL REGISTRATION
chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665.
Artificial Intelligence
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Humans
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Magnetic Resonance Imaging
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Neoplasm Staging
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Neural Networks, Computer
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Rectal Neoplasms/pathology*
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Retrospective Studies

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