1.Advances in the pharmacological mechanisms of monomers from Chinese medicine that target pathways involved in Alzheimer's dis-ease
Chengtian CHANG ; Zhihua LIU ; Shuaifang CHENG ; Xueke WANG ; Qianqian ZHAO ; Lit-ing GAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1417-1428
Alzheimer's disease(AD)is a preva-lent neurodegenerative disorder,characterized by the accumulation of beta-amyloid plaques,the phosphorylation of Tau proteins,and neuronal loss.As the global population ages,the incidence of AD is rising,and there is currently no effective cure.Herbal monomers have garnered interest due to their multifaceted pharmacological effects and low toxicity.This paper aims to provide a comprehen-sive overview of the mechanisms of Nrf2,NF-κB,PI3K/Akt,MAPK and other signalling pathways in the pathogenesis of AD.It also explores the modu-lation of these pathways by various TCM mono-mers,such as leptomeningine and tanshinone ⅡA,and details the research progress to date.For in-stance,Leptosine has been shown to activate Nrf2,thereby reducing oxidative stress,while Tanshinone ⅡA has been observed to inhibit the NF-κB path-way,leading to a reduction in inflammation.Not-withstanding the encouraging indications for the treatment of AD with TCM monomers,there are several challenges that must be addressed.Firstly,the precise mechanism of action remains to be ful-ly elucidated.Secondly,there are significant chal-lenges related to pharmacokinetics and bioavailabil-ity.Thirdly,the sample size of clinical studies is lim-ited and of variable quality.Fourthly,the quality control process is complex.Finally,interactions with other drugs must be taken into account.
2.Advances in the pharmacological mechanisms of monomers from Chinese medicine that target pathways involved in Alzheimer's dis-ease
Chengtian CHANG ; Zhihua LIU ; Shuaifang CHENG ; Xueke WANG ; Qianqian ZHAO ; Lit-ing GAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1417-1428
Alzheimer's disease(AD)is a preva-lent neurodegenerative disorder,characterized by the accumulation of beta-amyloid plaques,the phosphorylation of Tau proteins,and neuronal loss.As the global population ages,the incidence of AD is rising,and there is currently no effective cure.Herbal monomers have garnered interest due to their multifaceted pharmacological effects and low toxicity.This paper aims to provide a comprehen-sive overview of the mechanisms of Nrf2,NF-κB,PI3K/Akt,MAPK and other signalling pathways in the pathogenesis of AD.It also explores the modu-lation of these pathways by various TCM mono-mers,such as leptomeningine and tanshinone ⅡA,and details the research progress to date.For in-stance,Leptosine has been shown to activate Nrf2,thereby reducing oxidative stress,while Tanshinone ⅡA has been observed to inhibit the NF-κB path-way,leading to a reduction in inflammation.Not-withstanding the encouraging indications for the treatment of AD with TCM monomers,there are several challenges that must be addressed.Firstly,the precise mechanism of action remains to be ful-ly elucidated.Secondly,there are significant chal-lenges related to pharmacokinetics and bioavailabil-ity.Thirdly,the sample size of clinical studies is lim-ited and of variable quality.Fourthly,the quality control process is complex.Finally,interactions with other drugs must be taken into account.
3.Research progress of novel anti-VEGF therapy in the treatment of neovascular age-related macular degeneration with novel drugs
Huimin HOU ; Xueke CHANG ; Leying ZHANG ; Zongming SONG
China Pharmacist 2024;28(10):268-277
Neovascular age-related macular degeneration (nAMD) is one of the main causes of visual impairment in middle-aged and elderly people,and the incidence of this disease is rising in our country.The imbalance of vascular endothelial growth factor (VEGF) is the main cause of nAMD.In addition,various growth factors other than VEGF,complement system activation,inflammatory factors,autophagy,and many other factors are involved in the pathogenesis of nAMD.Currently,intravitreal injection of anti-VEGF drugs has become the first-line regimen for the treatment of nAMD,but there are still many shortcomings of the current anti-VEGF drugs,such as multiple potential risks of frequent injections,insensitive responses in some patients,and low compliance of the patients,etc.Therefore,the search for novel therapeutic agents has become urgent.This article provides a review of new developments in the study of novel drugs newly marketed and undergoing clinical trials for the treatment of nAMD,with the aim of seeking longer-lasting and better-acting therapeutic regimens,as well as exploring new therapeutic targets,to further inform the advancement of innovation and development of therapeutic strategies for nAMD.
4.Expression and Significance of SLAMF7 in Intestinal Tissue and Intestinal Inflammation in Mice
Yan YANG ; Xueke LU ; Xiuzhen GE ; Yunwei LOU ; Tingmin CHANG
Medical Journal of Peking Union Medical College Hospital 2024;15(4):831-838
To investigate the expression and significance of cell surface receptor signaling lymphocyte activation molecule family member 7 (SLAMF7) in normal intestinal tissues and intestinal inflammatory tissues of mice. Five C57BL/6J wild-type male mice aged 8-10 weeks were chosen and fed normally. Lamina propria lymphocytes (LPLs) and intestinal epithelial cells (IECs) were extracted, and totalcell RNA was extracted by Trizol reagent. The mRNA expression of SLAMF7 in cells was detected by reverse transcription polymerase chain reaction (RT-PCR) and real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Then 10 C57BL/6J wild-type male mice aged 8-10 weeks were randomly divided into control group ( Compared with colonic IECs, the expression of SLAMF7 was higher in colonic LPLs( SLAMF7 may play an important role in the occurrence and development of UC through neutrophil-related pathways.
5.The functional characteristics of frontoparietal network information integration and separation in patients with obsessive-compulsive disorder
Yibo GENG ; Hongxing ZHANG ; Xiaoyue WANG ; Yahui LIU ; Xiaoran WU ; Xueke WANG ; Qiaohua CHANG ; Qingjiang ZHAO ; Jiajia ZHANG ; Entu ZHANG ; Lunpu AI ; Haisan ZHANG
Chinese Journal of Psychiatry 2023;56(1):17-23
Objective:To explore the functional changes of brain network node information integration and separation in patients with obsessive-compulsive disorder (OCD) and its correlation with clinical symptoms.Methods:Fifty-six patients with obsessive-compulsive disorder (OCD group) and fifty-six healthy controls (control group) matched in gender, age and years of education were enrolled. All participants accepted resting-state functional magnetic resonance imaging scans of the whole brain. Yale-Brown Obsessive Compulsive Scale(Y-BOCS) was used to assess patients′ clinical symptoms. Based on graph theory and independent-sample t-test, the differences in functional network topological properties of nodes between the two groups were analyzed. Partial correlation analysis was used to discuss the relationship between the values of these properties and clinical symptoms. Results:Compared with the control group, the OCD group showed decreased global efficiency and increased shortest path length of the left superior temporal gyrus rostral area and right posterior central gyrus trunk region(both P<0.001, FDR corrected); decreased local efficiency( P=0.002, uncorrected) and clustering coefficient( P<0.001, FDR corrected) of the left inferior frontal gyrus dorsal region. Further analysis showed that the score of the global efficiency of the left superior temporal gyrus rostral area was positively correlated with the score of obsessive thoughts sub-scale ( r=0.390, P=0.005). The score of the shortest path length of the left superior temporal gyrus rostral area was negatively correlated with the obsessive thoughts sub-scale ( r=-0.359, P=0.010) in the OCD group. Conclusion:OCD patients have abnormal information integration and separation functions in the frontoparietal network(inferior frontal gyrus, posterior central gyrus) and abnormal information integration functions in the superior temporal gyrus rostral area. Higher global efficiency and shorter the shortest path length of the superior temporal gyrus rostral area suggest more obsessive thoughts in OCD patients.
6.The functional characteristics of frontoparietal network information integration and separation in patients with obsessive-compulsive disorder
Yibo GENG ; Hongxing ZHANG ; Xiaoyue WANG ; Yahui LIU ; Xiaoran WU ; Xueke WANG ; Qiaohua CHANG ; Qingjiang ZHAO ; Jiajia ZHANG ; Entu ZHANG ; Lunpu AI ; Haisan ZHANG
Chinese Journal of Psychiatry 2023;56(1):17-23
Objective:To explore the functional changes of brain network node information integration and separation in patients with obsessive-compulsive disorder (OCD) and its correlation with clinical symptoms.Methods:Fifty-six patients with obsessive-compulsive disorder (OCD group) and fifty-six healthy controls (control group) matched in gender, age and years of education were enrolled. All participants accepted resting-state functional magnetic resonance imaging scans of the whole brain. Yale-Brown Obsessive Compulsive Scale(Y-BOCS) was used to assess patients′ clinical symptoms. Based on graph theory and independent-sample t-test, the differences in functional network topological properties of nodes between the two groups were analyzed. Partial correlation analysis was used to discuss the relationship between the values of these properties and clinical symptoms. Results:Compared with the control group, the OCD group showed decreased global efficiency and increased shortest path length of the left superior temporal gyrus rostral area and right posterior central gyrus trunk region(both P<0.001, FDR corrected); decreased local efficiency( P=0.002, uncorrected) and clustering coefficient( P<0.001, FDR corrected) of the left inferior frontal gyrus dorsal region. Further analysis showed that the score of the global efficiency of the left superior temporal gyrus rostral area was positively correlated with the score of obsessive thoughts sub-scale ( r=0.390, P=0.005). The score of the shortest path length of the left superior temporal gyrus rostral area was negatively correlated with the obsessive thoughts sub-scale ( r=-0.359, P=0.010) in the OCD group. Conclusion:OCD patients have abnormal information integration and separation functions in the frontoparietal network(inferior frontal gyrus, posterior central gyrus) and abnormal information integration functions in the superior temporal gyrus rostral area. Higher global efficiency and shorter the shortest path length of the superior temporal gyrus rostral area suggest more obsessive thoughts in OCD patients.
7.Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors
Lidong WANG ; Liuyu LI ; Xin SONG ; Xueke ZHAO ; Fuyou ZHOU ; Ruihua XU ; Zhicai LIU ; Aili LI ; Jilin LI ; Xianzeng WANG ; Liguo ZHANG ; Fangheng ZHU ; Xuemin LI ; Weixing ZHAO ; Guizhou GUO ; Wenjun GAO ; Xiumin LI ; Lixin WAN ; Jianwei KU ; Quanxiao XU ; Fuguo ZHU ; Aifang JI ; Huixiang LI ; Jingli REN ; Shengli ZHOU ; Peinan CHEN ; Qide BAO ; Shegan GAO ; Haijun YANG ; Jinchang WEI ; Weimin MAO ; Zhanqiang HAN ; Zhiwei CHANG ; Yingfa ZHOU ; Xuena HAN ; Wenli HAN ; Lingling LEI ; Zongmin FAN ; Ran WANG ; Yuanze YANG ; Jiajia JI ; Yao CHEN ; Zhiqiang LI ; Jingfeng HU ; Lin SUN ; Yajie CHEN ; Helin BAI ; Duo YOU
Chinese Journal of Internal Medicine 2022;61(9):1023-1030
Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

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