1.Annual review of basic research on lung transplantation of China in 2024
Jier MA ; Junmin ZHU ; Lan ZHANG ; Xiaohan JIN ; Xiangyun ZHENG ; Senlin HOU ; Zengwei YU ; Yaling LIU ; Haoji YAN ; Dong TIAN
Organ Transplantation 2025;16(3):386-393
Lung transplantation is the optimal treatment for end-stage lung diseases and can significantly improve prognosis of the patients. However, postoperative complications such as infection, rejection, ischemia-reperfusion injury, and other challenges (like shortage of donor lungs) , limit the practical application of lung transplantation in clinical practice. Chinese research teams have been making continuous efforts and have achieved breakthroughs in basic research on lung transplantation by integrating emerging technologies and cutting-edge achievements from interdisciplinary fields, which has strongly propelled the development of this field. This article will comprehensively review the academic progress made by Chinese research teams in the field of lung transplantation in 2024, with a focus on the achievements of Chinese teams in basic research on lung transplantation. It aims to provide innovative ideas and strategies for key issues in the basic field of lung transplantation and to help China's lung transplantation cause reach a higher level.
2. Effects of HMGB1 on phenotypes, phagocytosis and ERK/JNK/P38 MAPK signaling pathway in dendritic cells
Ying-Ying CHEN ; Zhi-Xiang MOU ; Xiao-Long HU ; Yi-Yan ZHANG ; Jiao-Qing WENG ; Tian-Jun GUAN ; Ying-Ying CHEN ; Lan CHEN ; Tian-Jun GUAN ; Lan CHEN ; Pei-Yu LYU
Chinese Pharmacological Bulletin 2024;40(2):248-255
Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L
3.Exploration on bioactive equivalent combinatorial components of Xiaoke formula and its mechanism based on insulin resistance mice
Jian ZHANG ; Wen-juan MA ; Lin-jie DONG ; Jiang-lan LONG ; Yu ZHANG ; Dan YAN
Acta Pharmaceutica Sinica 2024;59(6):1698-1705
Xiaoke formula (XKF) is a classic formula for the treatment of insulin resistance (IR), but there is still unclear on bioactive equivalent combinatorial components (BECC) of XKF. In this study, based on the previous research of our team, three components, berberine, astragaloside IV and chlorogenic acid, were selected as the BECC of XKF, and their efficacy and mechanism were investigated. A high-fat diet-induced IR mouse model was used to detect blood glucose, insulin sensitivity, lipid metabolism, immune & inflammatory factors, etc., and staining of pathology sections was used to detect histopathological changes. Network pharmacology was used to predict the potential targets and signaling pathways of XKF and its BECC, and the results of the network were verified by Western blot. The animal welfare and experimental procedures followed the regulations of the Laboratory Animal Ethics Committee of Beijing MDKN Biotech Company (MDKN-2023-019). The results showed that BECC, which was composed of berberine, astragaloside IV and chlorogenic acid in the ratio of the original formula of XKF, was comparable to XKF in improving the glycemia, insulin sensitivity, histopathological damage, dyslipidemia, and immuno-inflammation in IR mice. The results of network pharmacology and Western blot suggested that the BECC of XKF and XKF might alleviate IR by promoting the activation of hepatic phosphatidylinositol 3-kinase (PI3K), phosphorylation of protein kinase B (AKT), and inhibiting the expression of glucose-6-phosphate phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1), the key limiting enzymes of hepatic gluconeogenesis. The above results suggest that berberine, astragaloside IV and chlorogenic acid can be used as the potential BECC of XKF to improve IR, and can regulate lipid metabolism, immuno-inflammation, and promote hepatic PI3K/AKT signaling to inhibit hepatic gluconeogenesis, regulate glucose homeostasis, and improve IR in mice.
4.KDM4A promotes the migration and invasion of breast cancer cell line MDA-MB-231 by downregulating BMP9
Yuanxiang CHEN ; Tao YU ; Shiyu YANG ; Tao ZENG ; Lan WEI ; Yan ZHANG
China Oncology 2024;34(2):176-184
Background and purpose:Exogenous bone morphogenetic protein 9(BMP9)inhibits the malignant progression of human breast cancer,but its expression is often abnormally low in breast cancer.In this study,we intended to explore the expression and role of epigenetically-modified histone lysine-specific demethylase 4A(KDM4A)in breast cancer,and to investigate the relationship between KDM4A and BMP9 and its possible regulatory mechanism.Methods:The expression of KDM4A in breast cancer and its relationship with BMP9 were analyzed by bioinformatics and verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Chromatin immunoprecipitation(ChIP)verified the regulatory role of KDM4A on BMP9,and RNA stability experiments and CHX protein stability experiments verified the effect of KDM4A in BMP9 expression.Exogenous recombinant MDA-MB-231 cells transfected with KDM4A small interfering RNA(siKDM4A)or infected with siBMP9 adenovirus(Ad-siBMP9)were constructed using RNA interference technology and adenoviruses knocking down BMP9,and the migratory and invasive abilities of the cells were detected by scratch healing assay and transwell assay,respectively.Results:Bioinformatics analysis showed that the expression of KDM4A was significantly higher in breast cancer than in normal tissues,and there was a negative correlation between the expression of KDM4A and that of BMP9 in breast cancer;RTFQ-PCR and Western blot showed that KDM4A was highly expressed in different breast cancer cell lines,and the knockdown of KDM4A significantly up-regulated BMP9.ChIP experiment confirmed that KDM4A could be significantly enriched in the promoter region of BMP9 gene,reducing its histone lysine 36 position instead of position 4 methyl status,thus silencing the expression of BMP9.RNA stability assay and CHX protein stability assay confirmed that KDM4A had no significant effect on the mRNA of BMP9,but could affect its protein degradation.After knocking down KDM4A,the migration and invasion abilities of breast cancer cells MDA-MB-231 were significantly inhibited,and this effect could be partially reversed by knocking down BMP9.Conclusion:KDM4A is highly expressed in breast cancer and breast cancer cell MDA-MB-231,and can silence its expression by down-regulating the level of histone methylation in the promoter region of the BMP9 gene,as well as affecting the stability of BMP9 at the protein level rather than at the level of mRNA,and promoting the migration and invasion of breast cancer.
5.Effectiveness analysis of hybrid endoscopic submucosal dissection in patients with colorectal epithelium-derived tumors
Yan GAO ; Xizhen SUN ; Yu LAN ; Chunzeng JIA
Chinese Journal of Internal Medicine 2024;63(1):46-52
Objective:To compare the clinical benefits of classic endoscopic submucosal dissection (ESD) and hybrid ESD for the treatment of colorectal epithelium-derived tumors.Methods:The current investigation was a retrospective multicenter study of 418 patients who underwent ESD between January 2015 and April 2021 at Beijing Jishuitan Hospital. The patients were assigned to one of two groups based on the surgical procedure they underwent; a classic ESD group or a hybrid ESD group. The primary outcome was the rate of en bloc resection and complete resection. SPSS 26.0 was used for statistical analysis. Homogeneity of variance was assessed via Cochran′s test. Normally distributed data with homogeneity of variance were analyzed via the t-test for independent samples. Non-normally distributed data and data with unequal variance were analyzed via the Kruskal-Wallis non-parametric test. Categorical data were analyzed via the Chi-square test or Fisher′s exact test. Multivariable assessment was performed via logistic regression analysis. Results:The en bloc resection rates [89.4% (84/94) vs. 87.0% (194/223), χ2=0.34, P=0.558] and complete resection rates [85.1% (80/94) vs. 82.1% (183/223), χ2=0.33, P=0.510] were similar. Compared with classic ESD, procedures were shorter in the hybrid ESD group [22(7, 213) vs. 47(12, 680) min, Z=0.23, P<0.001], dissection was completed more rapidly [0.14(0.02, 0.32) vs. 0.10(0.02, 0.41) cm 2/min, Z=0.08, P<0.001], and there was a higher rate of perforation (9.6% vs. 2.2%, χ2=2.67, P=0.006). Laterally spreading tumor granular type nodular mixed, non-granular type pseudo-depressed, flat-elevated type (odds ratio 2.826, P=0.012), and tumor location (odds ratio 6.970, P=0.005) were independently associated with complete resection in the hybrid ESD group. Conclusion:Classic ESD and hybrid ESD had similar en bloc and complete resection rates for colorectal epithelium-derived tumors, but hybrid ESD had shorter operation times. With respect to hybrid ESD, factors associated with failure of complete resection included lesion type and crossing tissue boundaries.
6.Research Advance of Chinese Medicine in Treating Atherosclerosis: Focus on Lipoprotein-Associated Phospholipase A2.
Lu-Ming WANG ; Wen-Lan ZHANG ; Nuan LYU ; Yan-Rong SUO ; Lin YANG ; Bin YU ; Xi-Juan JIANG
Chinese journal of integrative medicine 2024;30(3):277-288
As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
Humans
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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Medicine, Chinese Traditional
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Atherosclerosis/drug therapy*
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Lipoproteins
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Plaque, Atherosclerotic
;
Biomarkers
7.Discovery of the targets and lead compounds of traditional Chinese medicine based on the molecular trajectory of diabetes evolution
Yu ZHANG ; Jiang-lan LONG ; Ai-ting WANG ; Hao LÜ ; Ke-jun DENG ; Hao LIN ; Dan YAN
Acta Pharmaceutica Sinica 2024;59(8):2199-2204
Exploring the action targets (groups) of traditional Chinese medicine (TCM) is an important proposition to promote the innovation and development of TCM, but it has attracted a lot of attention as to whether it is related to the efficacy or the disease. Our team found that the metabolomic signature molecules in the development of diabetes mellitus (DM) were significantly associated with the clinical efficacy of Yuquan Pill through a large clinical sample study. Taking this as a clue, our team intends to expand the information on the omics features of DM development, and discover the key targets (groups) and their lead compounds for the hypoglycemic effect of Yuquan Pill. The project includes: ① Based on the retrospective clinical trials, using omics technology integrated with generative artificial intelligence, mining the characteristic information of proteome and microbiome, forming driving factors together with metabolome characteristic molecules, and characterizing the molecular trajectories of diabetes evolution and their interference by Yuquan Pill; ② Taking the evolving molecular trajectories as a link and pointer, using anthropomorphic modeling and molecular biology techniques such as chemical proteomics to discover the key targets (groups) of Yuquan Pill's hypoglycemic effect, with the prospective clinical samples for validation; ③ Evaluate the overall response of key targets (groups) using graph neural network technology, and search for drug-derived/endogenous lead compounds with proven clinical pathologies and clear mechanisms of action, so as to provide a new paradigm and technology for the discovery of complex active ingredient targets (groups) of TCM that are related to their clinical efficacy, as well as for the discovery of innovative medicines.
8.The Chinese guideline for management of snakebites
Lai RONGDE ; Yan SHIJIAO ; Wang SHIJUN ; Yang SHUQING ; Yan ZHANGREN ; Lan PIN ; Wang YONGGAO ; Li QI ; Wang JINLONG ; Wang WEI ; Ma YUEFENG ; Liang ZIJING ; Zhang JIANFENG ; Zhou NING ; Han XIAOTONG ; Zhang XINCHAO ; Zhang MAO ; Zhao XIAODONG ; Zhang GUOQIANG ; Zhu HUADONG ; Yu XUEZHONG ; Lyu CHUANZHU
World Journal of Emergency Medicine 2024;15(5):333-355
In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.
9.Clinical trial of Bailing capsules combined with ipratropium bromide in the treatment of patients with acute exacerabation of chronic obstructive pulmonary disease
Chen SHI ; Yu GAO ; Hong-Yan LIU ; Wen-Lan JI ; Ping HU
The Chinese Journal of Clinical Pharmacology 2024;40(3):317-320
Objective To observe the clinical efficacy and safety of Bailing capsules combined with compound ipratropium bromide solution inhalation in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods AECOPD patients were randomly divided into control group and treatment group.The control group was given compound ipratropium bromide 2.5 mL each time,3 times a day.On the basis of control group,the treatment group was given Bailing capsules 2.5 g,3 times a day,orally.Two groups were treated for 2 weeks.The clinical efficacy,forced vital capacity(FVC),arterial partial pressure of oxygen(PO2),serum levels of tumor necrosis factor-α(TNF-α),soluble intercellular adhesion molecule-1(sIC AM-1),soluble triggering receptor expressed on myeloid cells-1(sTREM-1)and adverse drug reactions were compared between two groups.Results Forty-nine patients were enrolled in both the treatment group and the control group,and no patients dropped out.After treatment,the total effective rates of treatment and control groups were 95.92%(47 cases/49 cases)and 83.67%(41 cases/49 cases)with significant difference(P<0.05).After treatment,FVC of the treatment and control groups were(2.89±0.41)and(2.66±0.35)L;PO2 were(83.39±8.02)and(76.78±7.55)mmHg;arterial partial carbon dioxide pressure were(48.47±5.11)and(56.02±6.42)mmHg;the levels of TNF-α were(41.14±6.03)and(69.64±8.29)ng·L-1;the levels of sICAM-1 were(327.52±31.19)and(420.20±38.88)μg·L-1;the levels of sTREM-1 were(31.14±3.22)and(38.85±5.29)ng·L-1;the differences were statistically significant(all P<0.05).The adverse drug reactions in treatment group were nausea and upper abdominal discomfort,which in control group were upper abdominal discomfort.The total incidences of adverse drug reactions in the treatment and control groups were 4.08%and 2.04%,without significant difference(P>0.05).Conclusion The clinical efficacy of Bailing Capsules combined with compound ipratropium bromide solution inhalation in the treatment of AECOPD patients is better than that of compound ipratropium bromide alone,without increasing the incidence of adverse drug reactions.
10.Bioequivalence study of ezetimibe tablets in Chinese healthy subjects
Pei-Yue ZHAO ; Tian-Cai ZHANG ; Yu-Ning ZHANG ; Ya-Fei LI ; Shou-Ren ZHAO ; Jian-Chang HE ; Li-Chun DONG ; Min SUN ; Yan-Jun HU ; Jing LAN ; Wen-Zhong LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2378-2382
Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90%CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90%CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

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