1.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
2.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
3.Therapeutic effect of anti-PD-L1&CXCR4 bispecific nanobody combined with gemcitabine in synergy with PBMC on pancreatic cancer treatment
Hai HU ; Shu-yi XU ; Yue-jiang ZHENG ; Jian-wei ZHU ; Ming-yuan WU
Acta Pharmaceutica Sinica 2025;60(2):388-396
Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8+ to CD4+ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8+ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).
4.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
5.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
6.Implications of left atrial volume index in patients with three-vessel coronary disease: A 6.6-year follow-up cohort study
Ru LIU ; Lei SONG ; Ce ZHANG ; Lin JIANG ; Jian TIAN ; Lianjun XU ; Xinxing FENG ; Linyuan WAN ; Xueyan ZHAO ; Ou XU ; Chongjian LI ; Runlin GAO ; Rutai HUI ; Wei ZHAO ; Jinqing YUAN
Chinese Medical Journal 2024;137(4):441-449
Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.
7.Targeting NUF2 suppresses gastric cancer progression through G2/M phase arrest and apoptosis induction
Bo LONG ; Huinian ZHOU ; Lixia XIAO ; Xiangyan JIANG ; Jian LI ; Zhijian MA ; Na HE ; Wei XIN ; Boya ZHANG ; Xiaoqin ZHU ; Zeyuan YU ; Zuoyi JIAO
Chinese Medical Journal 2024;137(20):2437-2451
Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.
8.Mechanism of Yanghe decoction inhibiting M2-type TAMs to promote migration invasion of triple-negative breast cancer cells based on EGF-EGFR signaling pathway
Cheng-Jie JIANG ; Le-Le TIAN ; Jin-Lei LUO ; Jian-Wei DOU ; Yan ZHANG
Chinese Pharmacological Bulletin 2024;40(11):2083-2092
Aim To explore the mechanism of Yanghe decoction-containing serum on the migration and inva-sion of MCF-7 breast cancer cells in a co-culture sys-tem with M2 tumor-associated macrophages(TAMs)based on the paracrine epidermal growth factor(EGF)/epidermal growth factor receptor(EGFR)sig-naling pathway.Methods The M2-type TAMs model was induced from THP-1 monocytic cell line through in vitro treatment with phorbol 12-myristate 13-acetate(PMA)and recombinant human macrophage colony-stimulating factor(M-CSF).The MCF-7 cells were co-cultured with M2-type TAMs using a Transwell non-contact co-culture system to evaluate their effects on migration and invasion.Subsequently,the cells were intervened with serum containing Yanghe decoction,and the proliferation of MCF-7 cells was detected using the CCK-8 assay,while their lateral migration ability was assessed through scratch assays.The invasion and vertical migration abilities of the cells were evaluated separately using Transwell assays,and the concentra-tion of EGF was measured using ELISA.Finally,the expression of EGFR,MCP-1,and MMP9 proteins was detected using Western blot.Results Compared to the control group,Yanghe decoction-containing serum in-hibited the proliferation of MCF-7 cells before and after co-culture.The serum reduced the scratch healing a-bility before and after co-culture and decreased their migration and invasion abilities.Additionally,Yanghe decoction-containing serum reduced the levels of EGF before and after co-culture and decreased the expres-sion of EGFR,MCP-1,and MMP9 proteins before and after+co-culture.Conclusion Yanghe decoction-containing serum can inhibit the migration and invasion of breast cancer MCF-7 cells before and after co-cul-ture with M2 TAMs.This effect may be related to the inhibition of the EGF-EGFR signaling pathway.
9.Advances in P-glycoprotein inhibitor research
Yi-Xin ZENG ; Jian-Dong JIANG ; Wei-Jia KONG
Chinese Pharmacological Bulletin 2024;40(12):2201-2206
Overexpression of P-glycoprotein(P-gp)is one of the major causes of therapeutic resistance to a variety of drugs,in-cluding antitumor drugs.P-gp has a wide range of substrates that are capable of expelling drugs from the cell via a twist-squeeze mechanism,leading to drug resistance.To address the problem of P-gp-mediated multidrug resistance,several inhibitors are being investigated.This article reviews the current small mole-cule compounds,natural source compounds and pharmaceutical excipients capable of inhibiting P-gp,and summarizes the cur-rent mechanisms of action of P-gp inhibitors,which are mainly competitive or non-competitive inhibition,stimulation of ATPase activity,down-regulation of expression,and metamorphic modu-lation.Currently,it is mainly the drug interactions and toxic re-actions that limit their clinical applications.
10.Percutaneous balloon mitral valvuloplasty guided by intracardiac echocardiography:a report of two cases
De-Jian LI ; Song CHEN ; Chao XU ; Xue JIANG ; Bo WANG ; Jian-Fei FENG ; Dong-Bang SONG ; Guo-Hui ZHANG ; Ming-Quan WANG ; Wei-Min WANG ; Da-Dong ZHANG
Chinese Journal of Interventional Cardiology 2024;32(5):295-297
For the past 30 years,percutaneous balloon mitral valve dilatation has been performed under the guidance of X-rays and bedside ultrasound.However,there are still some cases of mitral valve stenosis in the large atrium where balloon dilation failed.Intraperitoneal ultrasound-guided percutaneous balloon mitral valve plasty is accurate and feasible,which can reduce the occurrence of complications and improve the success rate of such elderly complex cases.Two patients with severe mitral stenosis underwent percutaneous balloon mitral valve plasty guided by intracardiac ultrasound.The operations were successful without any complications,which can provide reference for clinical treatment of mitral stenosis.

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