1.Immunodynamic changes in a mouse model of malignant pleural effusion
Xiao-Lei WEI ; Xu GUO ; Chuang-Xin ZHANG ; Qi WANG ; Xiao-Fan LIU ; Ming-Ming SHAO ; Huan-Zhong SHI ; Kan ZHAI
Laboratory Animal Research 2026;42(1):59-67
Background:
Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression.
Results:
The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity.
Conclusions
Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.
2.Mechanisms by which EPB41L4A-AS1 Influences Glial Cells-mediated Aβ Clearance
Li-xin NIU ; Xu-fei ZHANG ; Tian-zi LI ; Ming-hui LI ; Rui-xue YIN ; Zi-qiang WANG
Progress in Modern Biomedicine 2025;25(12):1942-1947
Objective:To explore the changes in the whole transcriptome gene expression profile affected by EPB41L4A-AS,and to reveal its potential mechanisms that influence the progression of AD.Methods:U251 cells with stable low expression of EPB41L4A-AS1 were constructed using shRNA technology.Transcriptome sequencing was performed to screen for transcripts regulated by EPB41L4A-AS1.KEGG pathway and GO analysis were used to explore the related signaling pathways and biological processes regulated by EPB41L4A-AS1.Immunofluorescence assay was used to investigate the effects of EPB41L4A-AS1 on the activity of glial cells with antibodies against GFAP.Results:Knocking down the expression of EPB41L4A-AS1 in U251 cells significantly influenced the levels of multiple transcripts,with 626 upregulated and 949 downregulated.Further analysis revealed that the downregulated transcripts are related to AD,activation and proliferation of glial cells,and formation of amyloid fibers,and close to multiple signaling pathways that are involved in the glial cells-mediated Aβ clearance.Cellular experiments have shown that EPB41L4A-AS1 regulated the synapses length and activity of glial cells.Conclusions:EPB41L4A-AS1 may influence the glial cells-mediated Aβ clearance through multiple signaling pathways.
3.Application of expanded carrier screening for autosomal recessive monogenic diseases in 1384 patients undergoing assisted reproductive technology
Ming SHI ; Xin KANG ; Lei WANG ; Chen ZHANG ; Yujie ZHANG ; Jingjing ZHANG ; Yang SHI ; Guanbin XU
Chinese Journal of Postgraduates of Medicine 2025;48(11):1020-1024
Objective:To explore the guiding significance of Expanded Carrier Screening (ECS) for the fertility process of individuals undergoing Assisted Reproductive Technology (ART) in Dalian.Methods:A retrospective analysis was conducted on the ECS results of patients who visited the Dalian Maternal and Child Health Care Center (Group) from January 2023 to June 2024. The study included the screening of 155 monogenic diseases and the ART status of carrier couples.Results:Among the 1 384 patient samples, 490 carriers were identified, yielding a detection rate of 35.41% (490/1 384). A total of 100 diseases and 91 pathogenic genes were detected. The most frequently identified disease was autosomal recessive hearing loss type 4 (SLC26A4), with a carrier rate of 3.54% (49/1384). For the 490 carriers, their partners were recalled for testing and, 322 partners participated. Eight high-risk couples were identified, accounting for 2.48% (8/322). Among the 322 couples, 4 used artificial insemination by husband (AIH, 1.24%, 4/322), 166 used in vitro fertilization (IVF, 51.55%, 166/322), 139 used intracytoplasmic sperm injection (ICSI, 43.17%, 139/322), and 1 underwent preimplantation genetic testing for monogenic diseases (PGT-M, 0.31%, 1/322). Twelve couples (3.73%, 12/322) did not undergo ART, were not pregnant, or chose gamete donation. Among the eight high-risk couples, three underwent IVF, four underwent ICSI, and one underwent PGT-M. One couple conceived through ICSI, and the fetus was followed up. Amniotic fluid Sanger sequencing revealed that the fetus had compound heterozygous mutations in the PAH gene, with two suspected pathogenic variants at c.532G>A and c.1174T>A. One couple undergoing PGT-M currently has one retrieved oocyte and zero usable blastocysts. The embryo carries a paternal mutation and is aneuploid.Conclusions:This study not only identified the common pathogenic diseases in Dalian, providing a reference for clinical treatment, but also validated the critical significance of ECS for individuals undergoing ART.
4.Study on the effectiveness and safety of a novel intravascular shock wave balloon for pre-treatment of severe coronary artery calcification lesions
Rui-tao ZHANG ; Zhen-yu TIAN ; Yong ZENG ; Guo-sheng FU ; Li XU ; Jian LIU ; Jian-ping LI ; Zhi-hui ZHANG ; Xin-qun HU ; Xiang CHENG ; Wen LU ; Ming CUI ; Yi-da TANG
Chinese Journal of Interventional Cardiology 2025;33(2):61-70
Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30%and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P<0.001],the degree of stenosis was significantly reduced[(13.24±6.60)%vs.(65.18±10.59)%,P<0.001].Procedural success was achieved in 100%of cases,and device success was 98.8%.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P<0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P<0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P<0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P<0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.
5.Mechanisms by which EPB41L4A-AS1 Influences Glial Cells-mediated Aβ Clearance
Li-xin NIU ; Xu-fei ZHANG ; Tian-zi LI ; Ming-hui LI ; Rui-xue YIN ; Zi-qiang WANG
Progress in Modern Biomedicine 2025;25(12):1942-1947
Objective:To explore the changes in the whole transcriptome gene expression profile affected by EPB41L4A-AS,and to reveal its potential mechanisms that influence the progression of AD.Methods:U251 cells with stable low expression of EPB41L4A-AS1 were constructed using shRNA technology.Transcriptome sequencing was performed to screen for transcripts regulated by EPB41L4A-AS1.KEGG pathway and GO analysis were used to explore the related signaling pathways and biological processes regulated by EPB41L4A-AS1.Immunofluorescence assay was used to investigate the effects of EPB41L4A-AS1 on the activity of glial cells with antibodies against GFAP.Results:Knocking down the expression of EPB41L4A-AS1 in U251 cells significantly influenced the levels of multiple transcripts,with 626 upregulated and 949 downregulated.Further analysis revealed that the downregulated transcripts are related to AD,activation and proliferation of glial cells,and formation of amyloid fibers,and close to multiple signaling pathways that are involved in the glial cells-mediated Aβ clearance.Cellular experiments have shown that EPB41L4A-AS1 regulated the synapses length and activity of glial cells.Conclusions:EPB41L4A-AS1 may influence the glial cells-mediated Aβ clearance through multiple signaling pathways.
6.Study on the effectiveness and safety of a novel intravascular shock wave balloon for pre-treatment of severe coronary artery calcification lesions
Rui-tao ZHANG ; Zhen-yu TIAN ; Yong ZENG ; Guo-sheng FU ; Li XU ; Jian LIU ; Jian-ping LI ; Zhi-hui ZHANG ; Xin-qun HU ; Xiang CHENG ; Wen LU ; Ming CUI ; Yi-da TANG
Chinese Journal of Interventional Cardiology 2025;33(2):61-70
Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30%and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P<0.001],the degree of stenosis was significantly reduced[(13.24±6.60)%vs.(65.18±10.59)%,P<0.001].Procedural success was achieved in 100%of cases,and device success was 98.8%.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P<0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P<0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P<0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P<0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.
7.Application review of wearable devices in auxiliary detection and diagnosis of acute mountain sickness
Hui-quan WANG ; Shuai MA ; Guo-sheng CHEN ; Yu GUO ; Jin-han YU ; Zheng-xu YAN ; Ming-hu LIU ; Xin-min DONG
Chinese Medical Equipment Journal 2025;46(9):100-107
The pathological mechanisms and related physiological indicators of acute mountain sickness(AMS)were introduced,and the present situation of wearable devices applied in AMS auxiliary detection and diagnosis were reviewed.The challenges and future development directions of wearable devices applied in auxiliary detection and diagnosis were pointed out.[Chinese Medical Equipment Journal,2025,46(9):100-107]
8.Application review of wearable devices in auxiliary detection and diagnosis of acute mountain sickness
Hui-quan WANG ; Shuai MA ; Guo-sheng CHEN ; Yu GUO ; Jin-han YU ; Zheng-xu YAN ; Ming-hu LIU ; Xin-min DONG
Chinese Medical Equipment Journal 2025;46(9):100-107
The pathological mechanisms and related physiological indicators of acute mountain sickness(AMS)were introduced,and the present situation of wearable devices applied in AMS auxiliary detection and diagnosis were reviewed.The challenges and future development directions of wearable devices applied in auxiliary detection and diagnosis were pointed out.[Chinese Medical Equipment Journal,2025,46(9):100-107]
9.Clinical effect analysis of rigid laryngoscopy performed in two body positions
Xin MA ; Ming LI ; Dingyuan XU ; Yujie WANG ; Xin XIN ; Bin WANG ; Wan LI
China Journal of Endoscopy 2025;31(8):55-60
Objective To explore the optimal body position of patients during rigid laryngoscopy.Methods 120 outpatients who underwent rigid laryngoscopy from December 2023 to March 2024 were divided into the conventional body position group(58 cases)and the anterior tilted position group(62 cases)by the random number table method.Patients in the conventional body position group were examined in the conventional body position(upright lower head position)and patients in the anterior tilted position group were examined in the anterior tilted position(body tilted forward by 60° and jaw lifted).The vocal folds were scored on the Friedman scale,the visual analogue scale(VAS)score was used to evaluate the comfortable degree of patients during the examination,the incidence of gag reflex sensitivity and the rate of complete pharyngeal exposure were compared between the two groups of patients.Results In the conventional body position group,there were 26 cases of Friedman's difficult exposure and 32 cases of easy exposure.The VAS scores of difficult exposure and easy exposure patients were 2.5(1.0,5.8)and 1.0(1.0,3.0),respectively;The incidence of gag reflex sensitivity was 42.3%and 34.4%,respectively;and the rates of complete pharyngeal exposure were 76.9%and 100.0%,respectively.In the anterior tilted position group,there were 28 cases of Friedman difficult exposure and 34 cases of easy exposure.The VAS scores of patients with difficult and easy exposure were 1.5(1.0,7.0)and 2.0(1.0,4.0),respectively;The incidence of gag reflex sensitivity was 46.4%and 29.4%,respectively;And the rates of complete pharyngeal exposure were 82.1%and 91.2%,respectively;The differences were not statistically significant(P>0.05).Conclusion When rigid laryngoscopy is performed in the upright lower head position or anteriorly tilted position,there is no significant difference in the comfortable degree scores,incidence of gag reflex sensitivity,and the rate of complete pharyngeal exposure in the patients in the two positions,and the examiners can choose the appropriate position according to their own examination habits.
10.Novel Structural Features of Isoflavone Synthase from Medicago truncatula Shed Light on Its Unique Enzymatic Mechanism
Chao SHI ; Zhao-Yang YE ; Fei XU ; Xiang-Ning DU ; Zhang-Xin CHEN ; Ming-Yue GU ; Jie DENG ; Wei WANG ; Liang-Yu LIU ; Mei-Ying WANG ; Xiao-Dong SU ; He-Li LIU ; Ming-Ying SHANG ; Li-Xin HUANG ; Zhen-Zhan CHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(8):1204-1213,中插1-中插6
Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

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