1.Study on the influencing factors of venetoclax trough concentration and its association with efficacy in patients with acute myeloid leukemia
Weiwei HE ; Zhirui LIU ; Shiwei QIN ; Qiang GONG ; Lin CHENG
China Pharmacy 2026;37(9):1200-1205
OBJECTIVE To investigate the effect of plasma trough concentration of venetoclax and its influencing factors in patients with acute myeloid leukemia (AML). METHODS After 5 days of venetoclax administration, venous blood samples were collected from AML patients before the next dose. Plasma trough concentrations of venetoclax were determined using high-performance liquid chromatography-tandem mass spectrometry. Spearman correlation was used to assess the correlations between venetoclax plasma trough concentration and various parameters (including patients’ general information, venetoclax-related indicators, liver function indicators, kidney function indicators, and blood routine indicators). Multiple linear regression analysis was performed to identify independent factors influencing plasma trough concentration of venetoclax. Using efficacy as dependent variable [complete remission (CR)+partial remission (PR) vs. no remission (NR)], univariate and multivariate binary Logistic regression analyses were conducted to identify factors affecting efficacy. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of venetoclax plasma trough concentration for clinical efficacy (assessed as CR). RESULTS A total of 172 venetoclax plasma trough concentration measurements from 101 patients were included in this study. The median plasma trough concentration of venetoclax was 2.38 (1.18, 3.85) μg/mL; the median sampling time for plasma trough concentration of venetoclax was 10 (7, 15) d; the duration of venetoclax use was (34±12) d. Multiple linear regression analysis showed that alkaline phosphatase ( B =14.65, 95%CI: 5.35-23.95, P =0.002), total bilirubin ( B =-101.71, 95%CI: -197.16 to -6.25, P =0.037), and white blood cell count ( B =-106.84, 95%CI: -187.61 to -26.07, P =0.010) were independent factors influencing plasma trough concentration of venetoclax. Due to patient attrition during treatment, 114 venetoclax plasma trough concentration measurements from 69 patients were included for efficacy evaluation. The results showed that 46 patients (66.7%) achieved CR, 11 patients (15.9%) achieved PR, and 12 patients (17.4%) were NR. Multivariate binary Logistic regression analysis showed that age, hemoglobin, venetoclax plasma trough concentration, hematocrit, and mean corpuscular hemoglobin were independent factors affecting patient efficacy ( P <0.05). ROC curve analysis showed that the cut-off value of plasma trough concentration of venetoclax for predicting patient efficacy (assessed as CR) was 1.68 μg/mL (AUC=0.66, 95%CI: 0.54-0.78, P =0.014). CONCLUSIONS There is considerable inter-individual variability in plasma trough concentration of venetoclax among AML patients. Plasma trough concentration of venetoclax is significantly correlated with alkaline phosphatase, total bilirubin, and white blood cell count. Plasma trough concentration of venetoclax is an independent factor affecting patient’s efficacy, and when the cut-off value for predicting CR is above 1.68 μg/mL, better effects may be achieved.
2.Parkin inhibits iron overload-induced cardiomyocyte ferroptosis by ubiquitinating ACSL4 and modulating PUFA-phospholipids metabolism.
Dandan XIAO ; Wenguang CHANG ; Xiang AO ; Lin YE ; Weiwei WU ; Lin SONG ; Xiaosu YUAN ; Luxin FENG ; Peiyan WANG ; Yu WANG ; Yi JIA ; Xiaopeng TANG ; Jianxun WANG
Acta Pharmaceutica Sinica B 2025;15(3):1589-1607
Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER T2 /Parkin fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.
3.High PRELID1 expression promotes epithelial-mesenchymal transition in gastric cancer cells and is associated with poor prognosis.
Xuan WU ; Jiamin FANG ; Weiwei HAN ; Lin CHEN ; Jing SUN ; Qili JIN
Journal of Southern Medical University 2025;45(7):1535-1542
OBJECTIVES:
To investigate the correlation of PRELID1 with gastric cancer (GC) progression, prognosis, and epithelial-mesenchymal transition (EMT) and the underlying mechanisms.
METHODS:
We analyzed the data of 115 patients undergoing radical gastrectomy for GC in our hospital between February, 2018 and March, 2023 to explore the correlation of PRELID1 expression level in GC tissues with tumor progression and patient prognosis. In cultured GC cells, the effects of lentivirus-mediated overexpression or interference of PRELID1 were observed on cell migration, invasion and EMT.
RESULTS:
Immunohistochemical staining revealed significantly higher PRELID1 expression in GC tissues (P<0.001), whose expression level was positively correlated with CEA ≥5 ng/mL (P=0.007), CA199 ≥37 U/mL (P=0.007), G3-4 stages (P=0.001), T3-4 stages (P=0.001), and N2-3 stages (P=0.020). Univariate and Cox multifactorial analysis showed that high PRELID1 level was an independent risk factor affecting 5-year survival of GC patients (P=0.001). In cultured GC cells, PRELID1 overexpression obviously promoted cell proliferation, migration, invasion, and the expressions of MMP2 and MMP9, and interference of PRELID1 produced the opposite changes. PRELID1 overexpression also increased the expressions of N-cadherin and vimentin and reduced the expression of E-cadherin. Mechanistic analyses showed that up-regulation of PRELID1 increased the expression of p-PI3K, p-AKT, and p-mTOR in GC cells, whereas its interference caused the opposite changes; the application of 740 Y-P, a PI3K/AKT pathway activator, significantly enhanced the migration, invasion, and EMT of GC cells with PRELID1 knockdown.
CONCLUSIONS
PRELID1 is highly expressed in GC and affects prognosis of the patients, and its high expression promotes migration, invasion and epithelial mesenchymal transition of GC cells possibly by activating the PI3K/AKT/mTOR pathway.
Humans
;
Stomach Neoplasms/metabolism*
;
Epithelial-Mesenchymal Transition
;
Prognosis
;
Cell Movement
;
Cell Line, Tumor
;
Male
;
Female
;
Middle Aged
;
Signal Transduction
;
Neoplasm Invasiveness
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
4.Expert Consensus on Perioperative Nursing Care for Follicular Unit Extraction(2025)
Chunhua ZHANG ; Weiwei BIAN ; Congmin WANG ; Lin SHEN ; Yong MIAO ; Na LIU ; Shan JIA ; Junhong AN ; Hongxia WANG ; Dongmei ZHANG
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1606-1613
To promote the standardization and normalization of perioperative care for follicular unit extraction(FUE) hair transplantation, ensure treatment efficacy, and align with advancements in the specialty, the Nursing Branch of the Chinese Association of Plastic and Aesthetics organized a panel of domestic experts. By integrating evidence-based medicine with clinical practice experience, and following thorough discussions, these experts developed the Clinical Practice
5.Effects and mechanisms study of anti-IL-13 monoclonal antibody on goblet cell hyperplasia in relieving acute laryngitis
Siyuan WAN ; Zhixing LIN ; Weiwei LIAO ; Lehui LI
International Journal of Laboratory Medicine 2025;46(2):168-174
Objective To investigate the effects and mechanisms of anti-IL-13 monoclonal antibody in alle-viating goblet cell metaplasia and hyperplasia in the treatment of acute subglottic laryngitis.Methods Periph-eral blood samples of children with acute subglottic laryngitis were collected and the children were divided into Mild group and Moderate-Severe group.Normal bronchial epithelial cells(NHBE cells)were cultured in vitro at the gas/liquid interface(ALI).Cell experiment were grouped as follows:Group-1(NHBE cell maintenance cultured group),Group-2(ciliated cell differentiation induction group),Group-3(IL-13 treatment group),and Group-4(IL-13+anti-IL-13 monoclonal antibody treatment group).The levels of inflammatory cytokines IL-10,IFN-γ and IL-13 in peripheral blood or cell culture supernatant were measured by enzyme linked immu-nosorbent assay(ELISA).The expression levels of goblet cell differentiation marker WGA and ciliary cell dif-ferentiation marker AAT,and the levels of phosphorylated(p-)ERK 1/2 and ERK 1/2 were determined by Western blot.The Cells diameter were measured by optical microscope.In vivo experiment,30 female C57BL/6J mice were randomly divided into Control group,Model group[(ovalbumin(OVA)and lipopolysaccharide(LPS)induced ashma mice model],and Model+anti-IL-13 antibody group(mice were treated intranasal with anti-IL-13 monoclonal antibody),10 mice in each group.Results Compared with Mild group,serum levels of IL-10,IFN-γ and IL-13 in Moderate-Severe group were increased(P<0.05).Compared with Group-1 cells,in Group-2 cells AAT expression was up-regulated(P<0.05).Compared with Group-1 cells,in Group-3 cells WGA expression was up-regulated(P<0.05),the levels of IL-10,IFN-γ,and IL-13 were increased(P<0.05),goblet cells diameters increased(P<0.05),and the levels of p-ERK 1/2 were up-regulated(P<0.05).Compared with Group-3,in Group-4 cells WGA expression were down-regulated(P<0.05).IL-10,IFN-γ,and IL-13 levels were decreased(P<0.05),goblet cells diameters decreased(P<0.05),and the levels of p-ERK 1/2 were down-regulated(P<0.05).There was no significant difference in the expression levels of ERK 1/2 among the four groups(P>0.05).In vivo animal experiment,compared with Control group,the bronchial inflammation score of the Model group mice was increased(P<0.05).Compared with Model group,the bronchial inflammation score of the Model+anti-IL-13 antibody group was decreased(P<0.05).Conclusion Anti-IL-13 monoclonal antibody can inhibit airway goblet cell metaplasia and hyperplasia,and may be used to relieve acute subglottic laryngitis.
6.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
7.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
8.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
9.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
10.Swift quantitative risk assessment of Vibrio parahaemolyticus in aquatic products of raw food
Hailin LI ; Weiwei ZHANG ; Yan LI ; Xiaohua LIN ; Qin ZHOU
Journal of Public Health and Preventive Medicine 2025;36(1):37-40
Objective To evaluate the disease risk of Vibrio parahaemolyticus (VP) in aquatic products of raw food in Guangzhou. Methods VP detection was carried out in aquatic products of raw food sold in Guangzhou from 2009 to 2022. Gene sequence and wgSNP analysis of 30 VP strains (including 15 food strains and 15 patient strains) were performed for the detection rate of pathogenic VP. sQMRA was applied to assess VP risk of aquatic products of raw food. Results The detection rate of VP in raw aquatic products in Guangzhou was 7.30% (98/1 343). The detection rate of TDH virulence gene in patient strains was 86.70% (13/15) , and the detection rate of TRH was 6.67% (1/15). In 15 food strains, TDH and TRH were negative. The WgSNP analysis showed that 2 food strains had high similarity with the patient strains, indicating the same cluster. Risk assessment showed that the number of Vibrio parahaemolyticus infection cases caused by intaking aquatic products of raw food in Guangzhou was 384 ever year. Conclusion The detection rate of VP in aquatic products of raw food is high in Guangzhou , and the detection rate of VP virulence genes in aquatic products of raw food is low. Gene sequence and wgSNP analysis can be used for risk assessment of food pathogenic bacteria. The risk of disease of Vibrio parahaemolyticus in aquatic products of raw food is high.


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