1.Research progress on material basis and mechanism of Hedyotis Dif-fusa-Scutellaria Barbata Herb Pair in the treatment of gastric cancer
Xiaowei ZHANG ; Nan WANG ; Mengge DAI ; Ruijuan LIU ; Ting MA
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(7):831-840
Gastric cancer is one of the most com-mon malignant tumors in the digestive system,which often occurs in middle-aged and elderly peo-ple.Traditional Chinese medicine recognizes gastric cancer as a kind of tumor characterized by fluid de-ficiency,heat accumulation and the growing bind-ing of toxins in the stomach.It is commonly treated with heat-clearing and detoxifying drugs in clinical practice.Hedyotis diffusa-Scutellaria barbata herb pair(HS)has the effects of clearing heat and detoxi-fying,promoting blood circulation,resolving car-buncle and expulsing boil,anti-inflammatory and analgesic,which are consistent with the etiology and pathogenesis of gastric cancer,therefore,it can be used for the treatment of gastric cancer.Modern pharmacological researches have con-firmed that HS can play an anti-gastric cancer role by inducing cell apoptosis,inhibiting cell prolifera-tion,inhibiting angiogenesis,improving immune mi-croenvironment and down-regulating telomerase activity.Herein,this review summarizes the active ingredients and related mechanism responsible for the anti-gastric cancer effect of HS,which will pro-vide the theoretical basis for its clinical use and the development of new drugs against gastric cancers.
2.The mediating effect of negative emotions between tumour psychological trait and psychosomatic status in patients with advanced lung cancer
Mengge LIU ; Binbin DENG ; Xuewei HUANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(11):1046-1051
Objective:To explore the relationship between tumour psychological trait, negative emotions, and psychosomatic status in patients with advanced lung cancer.Methods:A total of 261 patients with advanced lung cancer from January 2014 to March 2019 at the First Affiliated Hospital of Guangdong Pharmaceutical University and the Affiliated Cancer Hospital and Institute of Guangzhou Medical University were selected as the research subjects. General information questionnaire, tumour psychological scale(TPS), hospital anxiety and depression scale(HADS), and psychosomatic status scale for cancer patients(PSSCP)were utilized for cross-sectional investigation. Descriptive analysis and correlation analysis were performed using SPSS 26.0 statistical software. Structural equation modeling was conducted using AMOS 24.0, and the mediating effect was tested using the Bootstrap method.Results:The total score of TPS was 77.16±8.68. The total score of HADS was 16.67±3.81, and the sub-scale scores of anxiety and depression were 7.00±2.26 and 9.67±2.56.The total score of PSSCP was 37.09±4.99.Negative emotions were positively correlated with tumour psychological trait and psychosomatic status ( r=0.308, 0.390, both P<0.01), and tumour psychological trait was positively correlated with psychosomatic status ( r=0.478, P<0.01). The structural equation model demonstrated that negative emotions partially mediated the relationship between tumour psychological trait and psychosomatic status, accounting for 24.9%(0.217/0.870). Conclusion:The psychosomatic status is affected both directly by tumour psychological trait and indirectly through negative emotions.
3. Statin use and low-density lipoprotein cholesterol levels in patients aged 75 years and older with acute coronary syndrome in China
Yueyan XING ; Jing LIU ; Jun LIU ; Yongchen HAO ; Na YANG ; Mengge ZHOU ; Dong ZHAO
Chinese Journal of Cardiology 2019;47(5):351-359
Objective:
To assess the use of statins and low-density lipoprotein cholesterol (LDL-C) levels at admission in hospitalized patients aged 75 years and older with acute coronary syndrome (ACS) in China.
Methods:
Data used in this study derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a nationwide registry with 150 tertiary hospitals reporting details of clinical information of ACS patients. This study enrolled patients 75 years and older with ACS in CCC-ACS project from November 2014 to June 2017. Patients were divided into two groups according to the history of atherosclerotic cardiovascular disease (ASCVD). Pre-hospital statin use, LDL-C levels at admission and prescription of statins at discharge were reported.
Results:
A total of 10 899 patients 75 years and older with ACS were enrolled. The median age was 79 years and 58.7% (6 397 cases) were male. Among patients with history of ASCVD, 33.9% (1 028 cases) of them received statins before hospitalization. Among patients without history of ASCVD, 12.7% (996/7 871) received statins before hospitalization. The mean level of LDL-C was (2.4±0.9) mmol/L and LDL-C was <1.8 mmol/L in 24.7% (747 cases) of patients with history of ASCVD. The mean level of LDL-C was (2.6±0.9) mmol/L and LDL-C was <2.6 mmol/L in 51.7% (4 072 cases) of patients without history of ASCVD. At discharge, 91.2% (9 524/10 488) of patients were prescribed with statins in patients without contraindications for statin.
Conclusion
In elderly patients with recurrent ASCVD, there was an inadequate statin use before hospitalization and most patients did not reach the LDL-C target level when they had the recurrent events. In the elderly ACS patients without history of ASCVD, more than half of the patients had an ideal LDL-C level. It seems that ideal LDL-C level for primary prevention of ACS in elderly people needs to be reevaluated with further studies.
4.Classification of indeterminate thyroid nodules in preoperative fine needle aspiration by the combination of nuclear score and ultrasound features
Shurong HE ; Kan GAO ; Feiliang WANG ; Mengge WANG ; Rongming CHEN ; Weide DAI ; Lan CHEN ; Dongge LIU
Chinese Journal of Clinical and Experimental Pathology 2023;39(12):1441-1447
Purpose To assess the feasibility of nuclear score combined with ultrasound features on indeterminate thyroid nodules in fine needle aspiration cytological diagnosis.Methods A consecutive cohort of 119 thyroid fine-needle aspiration(FNA)specimens with indeterminate diagnosis(TBSRTC cate-gory Ⅲ-Ⅴ)and available histopathologic follow-up was evalua-ted.Original sonographic images and cytological slides of each nodule were reviewed by two experienced sonographers and two experienced cytopathologists respectively,and evaluated jointly to obtain consensus.The identification of the optimal cut-off points of simplified nuclear score and ultrasound features score for the diagnosis of malignancy or low-risk neoplasm were evalu-ated using the receiver operating characteristic(ROC)curves and the assessment of the area under the ROC curve(AUC).The specificity,sensitivity,positive predictive value(PPV)and negative predictive value(NPV)of nuclear score and US score were evaluated from crosstabs based on Cut-off points and signif-icance were calculated.The diagnostic accuracy of simplified nuclear score combined with ultrasound features was estimated by Logistic regression and ROC curve analysis.Results Nucle-ar grooves,intra-nuclear inclusions and chromatin clearing were more common in malignancy/low-risk neoplasms(P = 0.001,0.013 and 0.001 respectively).A Cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm,and the sensitivity was 99.1%.Nodule height greater than width,absent halo sign,irregular margin and absent intranodular vascularization were more common in malig-nancy/low-risk neoplasms(P = 0.003,0.007,0.003 and 0.004 respectively).When the Cut-off point was set as≥5,the PPV and specificity for defining malignancy/low-risk neoplasm were 95.9%and 78.6%respectively.ROC curve analysis showed that the diagnostic accuracy of nuclear score combined with US score(0.873,95%CI = 0.777-0.970)was higher than that of nuclear score alone(0.817,95%CI = 0.687-0.948,P =0.092)or US score alone(0.758,95%CI 0.637-0.879,P =0.047).But no significant difference was detec-ted between the combined score and the nuclear score.Conclu-sion The addition of simplified nuclear score and US score to FNA cytology can increase the diagnostic accuracy of cytology in indeterminate categories.
5.Influencing factors for prognoses of pulmonary adenocarcinoma patients with leptomeningeal metastases: a single-center study
Weifeng MA ; Milan ZHANG ; Tao ZHANG ; Mengge ZHANG ; Linlin JIA ; Yongshi TENG ; Shuhua DAI ; Huiqin LIU ; Yushu JIANG ; Lingzhi QIN ; Lipin YUAN ; Wei LI
Chinese Journal of Neuromedicine 2022;21(1):28-33
Objective:To investigate the prognoses of pulmonary adenocarcinoma patients with leptomeningeal metastases (LM) and explore their influencing factors.Methods:A retrospective analysis was performed. The clinical data, imaging features and treatment plans of pulmonary adenocarcinoma patients with LM admitted to our hospital from January 2010 to June 2021 were collected. Overall survival (OS) was used as the prognostic evaluation criterion and patients were divided into good prognosis group (OS≥6 months) and poor prognosis group (OS<6 months) accordingly. Logistic regression analysis was used to evaluate the influencing factors for prognoses of pulmonary adenocarcinoma patients with LM. These patients were grouped according to different Karnofsky performance status (KPS) scores and different treatment methods, and survival curves were drawn to compare their OS.Results:A total of 173 pulmonary adenocarcinoma patients with LM were enrolled in the study, including 75 with good prognosis and 87 with poor prognosis. There were significant differences in the KPS scores, pulmonary adenocarcinoma lesion controlled status, giving third generation tyrosine kinase inhibitor (TKI) therapy or not, giving systemic chemotherapy and/or whole brain radiotherapy or not between the two groups ( P<0.05). Multivariate Logistic regression analysis showed that KPS scores and pulmonary adenocarcinoma lesion controlled status were independent influencing factors for prognoses ( OR=4.186, 95%CI: 1.583-11.070, P=0.004; OR=4.198, 95%CI: 1.499-11.760, P=0.006). Survival curves showed median OS of 8.2 months for all patients ( 95%CI: 6.5-9.8). The OS in patients with low-risk(KPS scores≥60) was significantly higher than that in patients with high-risk(KPS scores<60), that in patients accepted TKI treatment was significantly higher than that in patients not accepted TKI treatment, and that in patients accepted TKI and systemic chemotherapy was significantly higher than that in patients accepted TKI alone ( P<0.05). Conclusion:Patients with high KPS scores and controlled pulmonary adenocarcinoma can have relatively good prognosis; TKI treatment and combination therapy may prolong OS of these patients.
6.BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period.
Zhenmeiyu LI ; Guoping LIU ; Lin YANG ; Mengge SUN ; Zhuangzhi ZHANG ; Zhejun XU ; Yanjing GAO ; Xin JIANG ; Zihao SU ; Xiaosu LI ; Zhengang YANG
Protein & Cell 2024;15(1):21-35
The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals
;
Mice
;
Humans
;
Ependymoglial Cells/metabolism*
;
Hedgehog Proteins/metabolism*
;
Ferrets/metabolism*
;
Cerebral Cortex
;
Neurogenesis
;
Mammals/metabolism*
;
Neuroglia/metabolism*
;
Bone Morphogenetic Protein 7/metabolism*
7.Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma.
Yingqiang LIU ; Zhengsheng ZHAN ; Zhuang KANG ; Mengyuan LI ; Yongcong LV ; Shenglan LI ; Linjiang TONG ; Fang FENG ; Yan LI ; Mengge ZHANG ; Yaping XUE ; Yi CHEN ; Tao ZHANG ; Peiran SONG ; Yi SU ; Yanyan SHEN ; Yiming SUN ; Xinying YANG ; Yi CHEN ; Shanyan YAO ; Hanyu YANG ; Caixia WANG ; Meiyu GENG ; Wenbin LI ; Wenhu DUAN ; Hua XIE ; Jian DING
Acta Pharmaceutica Sinica B 2023;13(12):4748-4764
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).