1.Platelet RNA signature independently predicts ovarian cancer prognosis by deep learning neural network model.
Chun-Jie LIU ; Hua-Yi LI ; Yue GAO ; Gui-Yan XIE ; Jian-Hua CHI ; Gui-Ling LI ; Shao-Qing ZENG ; Xiao-Ming XIONG ; Jia-Hao LIU ; Lin-Li SHI ; Xiong LI ; Xiao-Dong CHENG ; Kun SONG ; Ding MA ; An-Yuan GUO ; Qing-Lei GAO
Protein & Cell 2023;14(8):618-622
2.Discovery of novel covalent selective estrogen receptor degraders against endocrine-resistant breast cancer.
Yubo WANG ; Jian MIN ; Xiangping DENG ; Tian FENG ; Hebing HU ; Xinyi GUO ; Yan CHENG ; Baohua XIE ; Yu YANG ; Chun-Chi CHEN ; Rey-Ting GUO ; Chune DONG ; Hai-Bing ZHOU
Acta Pharmaceutica Sinica B 2023;13(12):4963-4982
Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα+) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα+ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.
3.Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study.
Yue GAO ; Chun-Jie LIU ; Hua-Yi LI ; Xiao-Ming XIONG ; Gui-Ling LI ; Sjors G J G IN 'T VELD ; Guang-Yao CAI ; Gui-Yan XIE ; Shao-Qing ZENG ; Yuan WU ; Jian-Hua CHI ; Jia-Hao LIU ; Qiong ZHANG ; Xiao-Fei JIAO ; Lin-Li SHI ; Wan-Rong LU ; Wei-Guo LV ; Xing-Sheng YANG ; Jurgen M J PIEK ; Cornelis D DE KROON ; C A R LOK ; Anna SUPERNAT ; Sylwia ŁAPIŃSKA-SZUMCZYK ; Anna ŁOJKOWSKA ; Anna J ŻACZEK ; Jacek JASSEM ; Bakhos A TANNOUS ; Nik SOL ; Edward POST ; Myron G BEST ; Bei-Hua KONG ; Xing XIE ; Ding MA ; Thomas WURDINGER ; An-Yuan GUO ; Qing-Lei GAO
Protein & Cell 2023;14(6):579-590
Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans
;
Female
;
Blood Platelets/pathology*
;
Biomarkers, Tumor/genetics*
;
Ovarian Neoplasms/pathology*
;
China
4.Mechanism of rhein inhibition of colorectal cancer through arginine metabolism based on protein chip
Zhi-hua WANG ; Wen-chang ZHANG ; Jie-yi HUANG ; Jian-chi LUN ; Yi-qing DING ; Wei-jie LÜ ; Xiao-long XU ; Shi-ning GUO
Acta Pharmaceutica Sinica 2022;57(8):2378-2387
Rhein is an anthraquinone compound extracted from rhubarb, aloe vera, Polygonum multiflorum. In this study, we screened the potential targets of rhein through protein chip technology and investigated the underlying mechanism of its inhibition of colorectal cancer. Colony formation assay and scratch assay were used to examine the effect of rhein on the proliferation and migration abilities of HCT116 cell; KEGG and protein interaction analyses of rhein specific binding proteins by screening rhein binding proteins using protein chip; qRT-PCR and Western blot assays were used to determine the effect of rhein on the expression levels of BCL-2-associated X protein (BAX), B-cell lymphoma-2 (BCL-2) and argininosuccinate synthetase 1 (ASS1) in HCT116 cell. The antitumor effect of rhein was verified by azoxymethane combined with dextran sodium sulfate (AOM/DSS) induced colorectal cancer model. Experimental animal procedures were performed in accordance with animal welfare and the standards of the Laboratory Animal Ethics Committee of South China Agricultural University, with approval from the ethics committee.
5.Nivolumab-associated pulmonary toxicities: a retrospective study based on FARES database from 2016 to 2019
Fang-yuan HU ; Ying-hong ZHAI ; Jin-fang XU ; Xiao-jing GUO ; Zhi-jian GUO ; Xiang ZHOU ; Yi ZHENG ; Li-jie CHI ; Xiao-fei YE ; Jia HE
Shanghai Journal of Preventive Medicine 2021;33(4):319-326
Objective:Nivolumab is one of the most common programmed death 1 (PD-1) inhibitors used as an immune checkpoint inhibitor (ICI). It brings significant therapeutic effects but often accompanied by serious drug toxicity. The pulmonary toxicities of nivolumab are not clear. This study aims to systematically explore the nivolumab-associated pulmonary toxicities and provide reference for clinical treatment. Methods:Data were extracted from US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 1, 2016 to September 30, 2019. Two types of disproportionality analysis, information component (IC) and reporting odds ratio (ROR), were applied in nivolumab-associated pulmonary adverse events (AEs) signal detection. Results:A total of 28 489 309 records were extracted from FAERS database and 8 181 records were associated with nivolumab. Analysis was conducted in 179 AEs and 86 signals were detected. Notably, potent signals were detected in radiation pneumonitis (IC025: 3.99, ROR025: 17.25), pneumonitis (IC025: 3.34, ROR025: 10.64) and bronchial fistula (IC025: 2.94, ROR025: 8.78). Nivolumab-associated pulmonary toxicities were more frequently reported in dyspnoea (IC025: 0.50, ROR025: 1.44), pneumonia (IC025: 0.08, ROR025: 1.07) and pneumonitis (IC025: 3.34, ROR025: 10.64). Results of IC and ROR methods were similar to each other. Most pulmonary toxicities were observed in patients with non-small cell lung cancer (
6.Chinese guideline for the application of rectal cancer staging recognition systems based on artificial intelligence platforms (2021 edition).
Yuan GAO ; Yun LU ; Shuai LI ; Yong DAI ; Bo FENG ; Fang-Hai HAN ; Jia-Gang HAN ; Jing-Jing HE ; Xin-Xiang LI ; Guo-Le LIN ; Qian LIU ; Gui-Ying WANG ; Quan WANG ; Zhen-Ning WANG ; Zheng WANG ; Ai-Wen WU ; Bin WU ; Ying-Chi YANG ; Hong-Wei YAO ; Wei ZHANG ; Jian-Ping ZHOU ; Ai-Min HAO ; Zhong-Tao ZHANG
Chinese Medical Journal 2021;134(11):1261-1263
7.No-tillage:core strategies for sustainable development of ecological agriculture of Chinese materia medica.
Kai SUN ; Xiu-Lian CHI ; Tie-Lin WANG ; Chuan-Zhi KANG ; Yan ZHANG ; Jian YANG ; Lu-Qi HUANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2021;46(8):1869-1875
Ecological agriculture is a crucial way for agriculture of Chinese materia medica, which emphasizes the application of ecological principles in the cultivation of traditional Chinese medicine. While long-term intensive farming and modern chemical agriculture have threatened soil health, the sustainable development of ecological agriculture of Chinese materia medica is constrained. No-til-lage can reduce both frequency and intensity of tillage. Compared with conventional agriculture, no-tillage can reduce soil disturbance, maintain no-tillage for a long or permanent period and keep mulching. The application of no-tillage has a long history. More and more studies have shown that no-tillage has many advantages over conventional tillage, and the ecological and economic benefits of no-tillage are particularly outstandingin long-term. The cultivation of Chinese medicinal materials adheres to the principle of not grabbing land from farmland, making full use of the soil resources under forests, mountains and wasteland. Reducing the risk of soil loss and sustai-nable utilization are the core issues in the process of new land cultivation. No-tillage application, which not only inherits the traditional Chinese concept of natural farming, but also integrates the laws of ecological agriculture, will become the core strategies of sustainable development of Chinese materia medica ecological agriculture. This study will introduce the basic concepts and development process of no-tillage, analyze their ecological benefits in ecological agriculture of Chinese materia medica, and put forward their application strategies.
Agriculture
;
China
;
Drugs, Chinese Herbal
;
Materia Medica
;
Medicine, Chinese Traditional
;
Sustainable Development
8.The effect of hematoma puncture drainage before decompressive craniectomy on the prognosis of hypertensive intracerebral hemorrhage with cerebral hernia at a high altitude.
Lin-Jie WEI ; Chi LIN ; Xing-Sen XUE ; Guo-Dong DUN ; Jian-Bo ZHANG ; Yan-Xiang TONG ; Jia-Xiong WANG ; Shi-Ji YANG ; Ling WANG ; Zhi CHEN ; Hua FENG ; Gang ZHU
Chinese Journal of Traumatology 2021;24(6):328-332
PURPOSE:
Rapid decompressive craniectomy (DC) was the most effective method for the treatment of hypertensive intracerebral hemorrhage (HICH) with cerebral hernia, but the mortality and disability rate is still high. We suspected that hematoma puncture drainage (PD) + DC may improve the therapeutic effect and thus compared the combined surgery with DC alone.
METHODS:
From December 2013 to July 2019, patients with HICH from Linzhi, Tibet and Honghe, Yunnan Province were retrospectively analyzed. The selection criteria were as follows: (1) altitude ≥1500 m; (2) HICH patients with cerebral hernia; (3) Glascow coma scale score of 4-8 and time from onset to admission ≤3 h; (4) good liver and kidney function; and (5) complete case data. The included patients were divided into DC group and PD + DC group. The patients were followed up for 6 months. The outcome was assessed by Glasgow outcome scale (GOS) score, Kaplan-Meier survival curve and correlation between time from admission to operation and prognosis. A good outcome was defined as independent (GOS score, 4-5) and poor outcome defined as dependent (GOS score, 3-1). All data analyses were performed using SPSS 19, and comparison between two groups was conducted using separate t-tests or Chi-square tests.
RESULTS:
A total of 65 patients was included. The age ranged 34-90 years (mean, 63.00 ± 14.04 years). Among them, 31 patients had the operation of PD + DC, whereas 34 patients underwent DC. The two groups had no significant difference in the basic characteristics. After 6 months of follow-up, in the PD + DC group there were 8 death, 4 vegetative state, 4 severe disability (GOS score 1-3, poor outcome 51.6 %); 8 moderate disability, and 7 good recovery (GOS score 4-5, good outcome 48.4 %); while in the DC group the result was 15 death, 6 vegetative state, 5 severe disability (poor outcome 76.5 %), 4 moderate disability and 4 good recovery (good outcome 23.5 %). The GOS score and good outcome were significantly less in DC group than in PD + DC group (Z = -1.993, p = 0.046; χ
CONCLUSION
PD + DC treatment can improve the good outcomes better than DC treatment for HICH with cerebral hernia at a high altitude.
Adult
;
Aged
;
Aged, 80 and over
;
Altitude
;
China
;
Decompressive Craniectomy
;
Drainage
;
Encephalocele/surgery*
;
Hematoma
;
Humans
;
Intracranial Hemorrhage, Hypertensive/surgery*
;
Middle Aged
;
Prognosis
;
Punctures
;
Retrospective Studies
;
Treatment Outcome
9.Effect of moxibustion at Feishu (BL 13) on airway inflammation in asthma model rats
Guo-Shan ZHANG ; Ran-Ran QIU ; Jiang PAN ; Jian ZHANG ; Chi ZHANG ; Cheng-Xi WANG ; Mi LIU
Journal of Acupuncture and Tuina Science 2020;18(3):165-173
Objective: To observe the effect of moxibustion at Feishu (BL 13) on related inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid of asthma model rats, and to explore the mechanism of moxibustion in treating asthma. Methods: A total of 48 Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, a moxibustion group and a medication group, with 12 rats in each group. Except for the normal group, the rats in the other three groups were subjected to ovalbumin sensitization to stimulate the asthma. At the same time, rats in the moxibustion group received moxibustion at bilateral Feishu (BL 13), and rats in the medication group received dexamethasone by intragastric administration. Rats in the normal and the model groups only received the same fixation and normal saline by intragastric administration. After the interventions, the inspiratory resistance, the expiratory resistance, and the pulmonary compliance were measured for rats in each group; the numbers of the inflammatory cells in the bronchoalveolar lavage fluid were counted; the levels of the involved inflammatory factors in bronchoalveolar lavage fluid were detected; the pathological morphologies of the lung tissues were observed under light microscope. Results: After modeling, compared with the normal group, the rats in the model group showed obvious asthma attack-like response, significantly increased inspiratory resistance and expiratory resistance (both P<0.01), and significantly reduced pulmonary compliance (P<0.01); thickened tracheal wall and the narrowed tracheal lumen observed under the light microscope; infiltration of inflammatory cells and increased eosinophils in and around the tracheal wall; significantly increased total number of inflammatory cells and proportion of eosinophils in the bronchoalveolar lavage fluid (all P<0.01); significantly reduced levels of interleukin (IL)-10, IL-12 and interferon (IFN)-γ (all P<0.01), and significantly increased levels of IL-4, IL-5 and tumor necrosis factor (TNF)-α (all P<0.01) in the bronchoalveolar lavage fluid. After intervention, compared with the model group, rats in the moxibustion and the medication groups showed significantly reduced asthma-like reaction, pathological morphological damage of lung tissue, inspiratory resistance and expiratory resistance (all P<0.01); significantly increased pulmonary compliance (P<0.01); significantly reduced total number of inflammatory cells, proportion of eosinophils, levels of IL-4, IL-5 and TNF-α in the bronchoalveolar lavage fluid (P<0.05 or P<0.01), while significantly increased IL-12 and IFN-γ levels (all P<0.01) in the bronchoalveolar lavage fluid; rats in the medication group also showed a significantly reduced IL-10 level in the bronchoalveolar lavage fluid (P<0.01); there was no statistically significant difference between the moxibustion and the medication groups (all P>0.05). Conclusion: Both moxibustion at Feishu (BL 13) and intragastric administration of dexamethasone can improve the asthma attack-like symptoms of ovalbumin-sensitized rats; regulating the inflammatory cell numbers and the inflammatory factor contents in the lung may be one mechanism of moxibustion in treating asthma.
10.Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.
Xiao-Ke LI ; Ming-Xiang ZHANG ; Feng-Zhen SHAO ; Da-Qiao ZHOU ; Jing-Dong XUE ; Tie-Jun LIU ; Xiao-Ling CHI ; Bing-Jiu LU ; Xian-Bo WANG ; Qin LI ; Jun LI ; De-Wen MAO ; Hua-Sheng YANG ; Hong-Zhi YANG ; Wen-Xia ZHAO ; Yong LI ; Guo-Liang ZHANG ; Yi-Ming ZHAO ; Jian-Dong ZOU ; Meng-Yang LIU ; Ke-Ke ZHANG ; Xian-Zhao YANG ; Da-Nan GAN ; Ying LI ; Peng ZHANG ; Zhi-Guo LI ; Shuo LI ; Yong-An YE
Chinese journal of integrative medicine 2020;26(5):330-338
OBJECTIVE:
To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients.
METHODS:
A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented.
RESULTS:
The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns.
CONCLUSION
Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Adenine
;
analogs & derivatives
;
therapeutic use
;
Adult
;
Antiviral Agents
;
therapeutic use
;
Double-Blind Method
;
Drug Therapy, Combination
;
Drugs, Chinese Herbal
;
therapeutic use
;
Female
;
Hepatitis B e Antigens
;
immunology
;
Hepatitis B, Chronic
;
drug therapy
;
immunology
;
Humans
;
Male
;
Medicine, Chinese Traditional
;
Organophosphonates
;
therapeutic use
;
Young Adult

Result Analysis
Print
Save
E-mail