1.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
2.Clinical Efficacy of Modified Huangqi Chifengtang in Treatment of IgA Nephropathy Patients and Exploration of Dose-effect Relationship of Astragali Radix
Xiujie SHI ; Meiying CHANG ; Yue SHI ; Ziyan ZHANG ; Yifan ZHANG ; Qi ZHANG ; Hangyu DUAN ; Jing LIU ; Mingming ZHAO ; Yuan SI ; Yu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):9-16
ObjectiveTo explore the dose-effect relationship and safety of high, medium, and low doses of raw Astragali Radix in the modified Huangqi Chifengtang (MHCD) for treating proteinuria in immunoglobulin A (IgA) nephropathy, and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy, diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity, were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo, while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix (60, 30, 15 g). Each group contained 30 patients, and the treatment period was 12 weeks. Changes in 24-hour urinary protein (24 hUTP), traditional Chinese medicine (TCM) syndrome scores, effective rate, and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment, 24 hUTP significantly decreased in the high, medium, and low-dose groups, as well as the control group (P<0.05, P<0.01). The TCM syndrome scores in the high, medium, and low-dose groups also significantly decreased (P<0.01). Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium, low-dose, and control groups (P<0.05, P<0.01), and the 24 hUTP in the medium-dose group was significantly lower than in the control group (P<0.05). The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups (P<0.05, P<0.01). The total effective rates for proteinuria in the high, medium, low-dose, and control groups were 92.59% (25/27), 85.19% (23/27), 60.71% (17/28), and 57.14% (16/28), respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups (χ2=13.185, P<0.05, P<0.01). The effective rates for TCM syndrome scores in the high, medium, low-dose, and control groups were 88.89% (24/27), 81.48% (22/27), 71.43% (20/28), and 46.43% (13/28), respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group (χ2=14.053, P<0.01). Compared with pre-treatment values, there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However, eGFR significantly decreased in the low-dose and control groups after treatment (P<0.05), and serum creatinine levels increased significantly in the control group (P<0.05). No statistically significant differences were observed in urea nitrogen, uric acid, albumin, total cholesterol, triglycerides, liver function, and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high, medium, and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.
3.Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study
Weiyu ZHANG ; Huixin LIU ; Ming LIU ; Shi YING ; Renbin YUAN ; Hao ZENG ; Zhenting ZHANG ; Sujun HAN ; Zhannan SI ; Bin HU ; Simeng WEN ; Pengcheng XU ; Weimin YU ; Hui CHEN ; Liang WANG ; Zhitao LIN ; Tao DAI ; Yunzhi LIN ; Tao XU
Chinese Medical Journal 2024;137(11):1324-1331
Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.
4.BMP9 down-regulates HIF-1α to inhibit aerobic glycolysis,migration and invasion of breast cancer MDA-MB-231 cells
Tao YU ; Yuan-Xiang CHEN ; Shi-Yan LIU ; Huo-Mei YU ; De-Yu LIAO ; Shi-Yu YANG ; Tao ZENG ; Lan WEI ; Yan ZHANG
Chinese Pharmacological Bulletin 2024;40(5):840-846
Aim To investigate the effects of bone-forming protein BMP9 on aerobic glycolysis,migration and invasion ability in triple-negative breast cancer MDA-MB-231 cells and the underlying mechanisms.Methods The experimental group infected MDA-MB-231 cells with human BMP9 recombinant adenovirus(AdBMP9),while the control group infected cells with empty GFP adenovirus.Lactate,glucose and ATP as-say kits were used to detect glucose uptake,lactate and ATP production.The correlation between BMP9 and key glycolytic enzyme genes in pancarcinoma was ana-lyzed using GEPIA2 database.The mRNA expression levels of GLUT1,HK2,PKM2 and LDHA in MDA-MB-231 cells after overexpression of BMP9 were detec-ted by qRT-PCR.Potential targets of BMP9 inhibiting MDA-MB-231 aerobic glycolysis were analyzed in STRING database.The expression levels of HIF-1αand downstream protein were detected by Western blot.The changes of cell migration and invasion ability after different treatments were evaluated by the scratch heal-ing assay and Transwell assay.Results Compared with the control group,BMP9 down-regulated glucose uptake,lactate production,ATP level(P<0.01),and inhibited HIF-1α and its downstream protein ex-pression in MDA-MB-231 cells.Overexpression of HIF-1α in rescue experiment reversed the inhibitory effect of BMP9 on aerobic glycolysis,migration and in-vasion of MDA-MB-231 breast cancer cells.Conclu-sion BMP9 down-regulates HIF-1α to inhibit the aer-obic glycolysis and migration and invasion ability of MDA-MB-231 breast cancer cells.
5.SNHG3-mediated autophagy promotes proliferation,migration and invasion of breast cancer cells
Yuan-Xiang CHEN ; Huo-Mei YU ; Shi-Yan LIU ; De-Yu LIAO ; Tao YU ; Shi-Yu YANG ; Tao ZENG ; Yan ZHANG
Chinese Pharmacological Bulletin 2024;40(6):1097-1104
Aim To investigate the effects of autophagy regula-ted by LncRNA SNHG3 on the proliferation,migration,invasion and EMT of human breast cancer cell line MCF-7.Methods The expression of SNHG3 in breast cancer and breast cancer cell line MCF-7 was analyzed by bioinformatics and real-time fluores-cent quantitative PCR(RT-qPCR);RNAi technology was used to construct MCF-7 recombinant cell lines with knockdown SNHG3(siSNHG3)and control(siNC),and Western blot and cellular immunofluorescence were applied to detect autophagy markers;autophagosome lysosomal fusion inhibitor BafA1 or ear-ly autophagosome formation inhibitor 3-MA was employed to treat MCF-7 cells with or without SNHG3 knockdown,Western blot was used to detect the expression of LC3-Ⅱ or p62,and the effect on autophagic vesicle formation or autophagic degradation was observed;clone formation experiment,CCK8 experiment,wound healing experiment,and Transwell experiment were used to detect the effects of siSNHG3 combined or not combined with BafA1 or 3-MA on the proliferation,lateral migration,longitudi-nal migration,and invasion of MCF-7 cells.Western blot was used to detect its effect on the EMT of MCF-7 cells.Results Bioinformatics analysis and RT-qPCR confirmed that SNHG3 was highly expressed in breast cancer and breast cancer cell line MCF-7;Western blot and cellular immunofluorescence confirmed that knockdown of SNHG3 could activate autophagy in breast cancer;the clone formation,CCK-8,wound healing,and Tran-swell experiment confirmed that downregulation of SNHG3 ex-pression could inhibit tumor proliferation,migration,and inva-sion by activating autophagy;Western blot confirmed that SNHG3 promoted EMT process of breast cancer through negative regulation of autophagy.Conclusions SNHG3 is abnormally overexpressed in breast cancer and negatively regulates autoph-agy,and can enhance the proliferation,migration,invasion and EMT process of breast cancer cells through negatively regulating autophagy,suggesting that SNHG3 is a potential target for diag-nosis and treatment of breast cancer.
6.Study on mechanism of Tibetan medicine Rhodiola crenulata in treatment of cerebral microcirculatory disorders based on network pharmacology and experimental validation in rats
Si-Qing MA ; Yu-Jing SHI ; Yuan-Bai LI ; Yang YANG ; Meng LI ; Yu DU ; Yi-Hao LI ; Fang-Zhou LIU
Chinese Pharmacological Bulletin 2024;40(9):1781-1791
Aim To explore the core target,key com-ponents and mechanism of Tibetan medicine Rhodiola crenulata in improving cerebral microcirculation based on literature research,network pharmacology,molecu-lar docking and experimental verification.Methods The chemical components of Rhodiola were collected through literature and database,and the potential tar-gets of Rhodiola crenulata were predicted by reverse pharmacophore matching.The related targets of cere-bral microcirculation disorder were obtained and targets were mapping with Rhodiola crenulata.PPI network was constructed and the core targets were screened.The regulatory network of"herb-component-target-dis-ease"was constructed and key components were screened.GO and KEGG enrichment analysis were conducted,and a"Core target-Pathway-Biological Process"network was constructed.Finally,molecular docking validation was carried out,and RT-qPCR and Western blot were used for animal experiments to fur-ther confirm the results of network pharmacology analy-sis.Results A total of 76 active components of Rhodiola crenulata were obtained and corresponding to 285 targets.Altogether 1074 related targets related to cerebral microcirculation disorder were obtained.A-mong them,there were 97 common targets and the main core targets were 6.The key components were 6.The results of molecular docking showed that the bind-ing activity of three key components to the core target was greater than that of the core target protein and its original ligand.The result of RT-qPCR and Western blot demonstrated that Tibetan medicine Rhodiola cre-nulata could significantly reduce the expression of core target CASP3 and AKT1(P<0.01).Conclusions Tibetan medicine Rhodiola crenulata can improve the cerebral microcirculation disorder through multi compo-nents,multi targets and multi pathways.This study provides an experimental basis for clinical application of Tibetan medicine Rhodiola crenulata to treat cerebral microcirculation disorder.
7.Effects of astragalus angelica on apoptosis and expression of Bax and caspase-3/9 in rabbit chondrocytes after fresh osteochondral allograft
Wan-Tao DONG ; Pan YANG ; Xiu-Juan YANG ; Shi-Ming QIU ; Peng YUAN ; Jing-Yi LIU ; Jiu-Mei HUANG ; Yu ZHOU
Chinese Pharmacological Bulletin 2024;40(12):2288-2294
Aim To observe the effect of Astragalus membranaceus and Angelica sinensis on the apoptosis of chondrocytes,and to investigate the effect of Astrag-alus membranaceus and Angelica sinensis on the sur-vival of fresh ostecartilage allograft.Methods Forty-eight 4-month-old New Zealand white rabbits,half male and half female,were randomly divided into sham operation group,model group,positive group and As-tragalus and Angelica 5∶1 group.In addition to the sham operation group,the other groups were both male and female donors and recipients for knee joint osteo-cartilage cross transplantation modeling.After 8 weeks of drug intervention,samples were taken for general observation,HE staining,saffrane-O staining,immu-nohistochemical staining,qPCR and Western blot de-tection.Results Compared with model group,As-tragalus and Angelica 5∶1 group and positive group,the repair site healed better,the morphology of osteo-chondrocytes tended to be normal,and the division and proliferation were obvious.Proteoglycan deposition in-creased and type Ⅱ collagen content was higher,the differences were statistically significant(P<0.05).qPCR and Western blot results showed that compared with model group,the mRNA and protein expressions of Bax,caspase-3 and caspase-9 in other groups were significantly decreased(P<0.05).Conclusion As-tragalus and Angelica can promote the survival of fresh osteochondral allograft,and its mechanism may be re-lated to promoting collagen production,promoting chondrocyte proliferation and inhibiting chondrocyte apoptosis.
8.Progress in research on risk assessment models for cancer-associated thrombosis
Haoran SHI ; Qiaodan LU ; Yuan XU ; Xiaojie WANG ; Haibo DENG ; Lei WANG ; Jianhua SUN ; Yu WANG ; Liyun ZHU ; Ranxun AN ; Xinyi ZHOU ; Yufen MA
Chinese Journal of Modern Nursing 2024;30(8):1010-1017
Cancer-associated thrombosis (CAT) is a common complication and cause of death in cancer patients. Accurately and efficiently identifying high-risk groups for CAT using risk assessment models and implementing targeted early prevention is key. Although numerous CAT risk assessment models currently exist, their predictive capabilities vary across different populations. This article provides a comprehensive review of CAT risk assessment models and their application status, aiming to offer a reference for clinical nursing staff to understand and choose appropriate risk assessment tools.
9.Development of the Cancer-associated Thrombosis Prevention Knowledge, Attitude and Practice Questionnaire for Nurses and its reliability and validity tests
Haoran SHI ; Yuan XU ; Xiaojie WANG ; Haibo DENG ; Lei WANG ; Jianhua SUN ; Yu WANG ; Liyun ZHU ; Qiaodan LU ; Ranxun AN ; Xinyi ZHOU ; Yufen MA
Chinese Journal of Modern Nursing 2024;30(16):2124-2130
Objective:To develop the Cancer-associated Thrombosis (CAT) Prevention Knowledge, Attitude and Practice Questionnaire for Nurses, and conduct reliability and validity tests.Methods:This study was a questionnaire development study. Guided by the theory of knowledge, attitude, and practice, an initial CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses was formed through literature review, group discussion, two rounds of expert consultation, and pre-survey. From April to May 2023, convenience sampling was used to select 700 in-service nurses from Chinese Academy of Medical Sciences & Peking Union Medical College as the research subject, and the reliability and validity of the questionnaire were tested.Results:A total of 700 questionnaires were distributed, and 593 valid questionnaires were collected, with a valid response rate of 84.71% (593/700). The final version of the CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses included three dimensions of knowledge, attitude, and practice, with a total of 39 items. The scale-level content validity index ( S- CVI) was 1.000, with an average S- CVI of 0.971 and an item-level CVI (I- CVI) of 0.860 to 1.000. Exploratory factor analysis extracted a total of seven common factors, with a cumulative variance contribution rate of 77.376%. The total Cronbach's α coefficient of the questionnaire was 0.937, and the Cronbach's α coefficients for each dimension were 0.923, 0.987, and 0.979. The half reliability coefficient was 0.984. After two weeks, the reliability coefficients for each dimension of retesting were 0.959, 1.000, and 0.994. Conclusions:The CAT Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses developed in this study has good reliability and validity, and can be used as an evaluation tool for the cognition of clinical nurses in CAT prevention.
10.Investigation of tick species and potential pathogenic ricks in certain areas of Wuwei City,Gansu Province
Rui-Shan LI ; Zhen HE ; Xiang YUAN ; Shi-Wei SUN ; Yi-Wen LIU ; Wen-Kai ZHANG ; Lin ZHANG ; Yu-Hua WANG ; Zhen-Hua LU ; Zhao-Hua JI ; Zhong-Jun SHAO
Chinese Journal of Zoonoses 2024;40(4):328-333
To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.

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