1.Erratum: Author correction to "PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism" Acta Pharm Sin B 13 (2023) 157-173.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2025;15(4):2297-2299
[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].
2.Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy.
Chao CHEN ; Shiyu DU ; Qianglan LU ; Xueting SHEN ; Shuai DING ; Lihua QU ; Yamei GAO ; Zhiqiang YIN ; Zhe LI ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2025;15(10):5431-5443
Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C2P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn2+ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C2P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.
3.Exploration of the Etiology,Pathogenesis and Syndrome Differentiation in the Treatment of Liver Cancer by Renowned Traditional Chinese Medicine Practitioner Changquan Ling from the Perspective of"Dispersing Qi and Fortifying the Body Resistance"
Mingxing ZHU ; Yuqian WANG ; Jue YANG ; Yufei ZHANG ; Jiaojiao CHEN ; Yujun LUO ; Huiling ZHOU ; Rui HAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(3):717-723
Hepatocellular carcinoma(HCC),as the most common type of liver cancer,poses a significant threat to global public health due to its high incidence and mortality rates.This paper delves into the etiology,pathogenesis,and syndrome differentiation of liver cancer from the perspective of"dispersing qi and fortifying the body resistance",based on the clinical experience of renowned traditional Chinese medicine(TCM)practitioner,Prof.Changquan Ling.Prof.Ling believes that the development of liver cancer is closely related to the disruption of liver qi flow,the accumulation of blood stasis over time,and the generation of toxin from long-term stagnation,accompanied by pathological changes such as imbalance of yin and yang,deficiency of the body's vital qi and accumulation of pathogenic factors,and internal blazing of cancer toxins.In terms of treatment,he emphasizes the principles of dispersing qi and fortifying the body resistance,addressing both the root cause and symptoms.This is achieved by regulating the functions of viscera,improving the stagnation of qi flow,and supplemented by methods such as clearing heat and detoxifying,and softening and dispersing hard masses,aiming to break the vicious cycle of qi stagnation,deficiency of vital qi,and pathogenic factor generation,thereby promoting the recovery from the disease.Through detailed analysis of clinical cases,this paper demonstrates Prof.Ling's unique insights and significant efficacy in treating liver cancer through"dispersing qi"to"fortify the body resistance",ultimately achieving"tumor suppression".This provides new references and perspectives for the clinical diagnosis and treatment of liver cancer in TCM.
4.Exploration of the Etiology,Pathogenesis and Syndrome Differentiation in the Treatment of Liver Cancer by Renowned Traditional Chinese Medicine Practitioner Changquan Ling from the Perspective of"Dispersing Qi and Fortifying the Body Resistance"
Mingxing ZHU ; Yuqian WANG ; Jue YANG ; Yufei ZHANG ; Jiaojiao CHEN ; Yujun LUO ; Huiling ZHOU ; Rui HAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(3):717-723
Hepatocellular carcinoma(HCC),as the most common type of liver cancer,poses a significant threat to global public health due to its high incidence and mortality rates.This paper delves into the etiology,pathogenesis,and syndrome differentiation of liver cancer from the perspective of"dispersing qi and fortifying the body resistance",based on the clinical experience of renowned traditional Chinese medicine(TCM)practitioner,Prof.Changquan Ling.Prof.Ling believes that the development of liver cancer is closely related to the disruption of liver qi flow,the accumulation of blood stasis over time,and the generation of toxin from long-term stagnation,accompanied by pathological changes such as imbalance of yin and yang,deficiency of the body's vital qi and accumulation of pathogenic factors,and internal blazing of cancer toxins.In terms of treatment,he emphasizes the principles of dispersing qi and fortifying the body resistance,addressing both the root cause and symptoms.This is achieved by regulating the functions of viscera,improving the stagnation of qi flow,and supplemented by methods such as clearing heat and detoxifying,and softening and dispersing hard masses,aiming to break the vicious cycle of qi stagnation,deficiency of vital qi,and pathogenic factor generation,thereby promoting the recovery from the disease.Through detailed analysis of clinical cases,this paper demonstrates Prof.Ling's unique insights and significant efficacy in treating liver cancer through"dispersing qi"to"fortify the body resistance",ultimately achieving"tumor suppression".This provides new references and perspectives for the clinical diagnosis and treatment of liver cancer in TCM.
5.Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.
Yongchun PAN ; Xiaowei LUAN ; Fei ZENG ; Xuyuan WANG ; Shurong QIN ; Qianglan LU ; Guanzhong HE ; Yanfeng GAO ; Xiaolian SUN ; Xin HAN ; Bangshun HE ; Yujun SONG
Acta Pharmaceutica Sinica B 2024;14(2):795-807
Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.
6.Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234.
Zekun LI ; Yongchun PAN ; Shiyu DU ; Yayao LI ; Chao CHEN ; Hongxiu SONG ; Yueyao WU ; Xiaowei LUAN ; Qin XU ; Xiaoxiang GUAN ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2024;14(2):897-899
[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].
7.Effect of intradialytic hypotension on brain components, cognition, emotion, and life ability in maintenance hemodialysis patients
Rongrong HU ; Yujun QIAN ; Tianye LIN ; Fei HAN ; Jing YUAN ; Feng FENG ; Yicheng ZHU ; Xuemei LI ; Ke ZHENG
Chinese Journal of Nephrology 2024;40(10):771-779
Objective:To explore the impact of intradialytic hypotension (IDH) on brain component volume, as well as its relationship with depression and cognitive function changes in maintenance hemodialysis patients.Method:It was a cross-sectional observational study. Clinical data of 119 patients under maintenance hemodialysis in Peking Union Medical College Hospital from July 2013 to July 2014 were collected, retrospectively. Patients were divided into IDH group and non-IDH group. 3.0T Magnetic resonance imaging examination of the head for all patients was completed and the results of volume analysis of each component of the brain were extracted. Cognitive function was assessed by the Chinese version of the simplified mental state examination scale (C-MMSE) and the Chinese version of the Montreal cognitive assessment scale (C-MoCA). Depressive status was assessed by the Hamilton depression scale 17 (HAMD_17) and living ability was assessed by the Alzheimer's disease collaborative study-daily living ability assessment questionnaire. In addition, the Philadelphia word learning test was used to measure memory, the Boston naming test to measure language, the connection test A and B to measure executive ability, and the Stroup test C to measure attention. The differences in brain component volume, cognitive function, emotion, and life ability between two groups of patients were compared, and the correlation between IDH and brain component volume was explored by regression analysis.Result:A total of 119 patients were included in this study, of whom 22 (18.5%) had hypotension during dialysis. The volumes of amygdala, cuneiform lobe, and posterior cingulate gyrus in IDH group were significantly smaller than those in the non-hypotension group [ (1.6±0.2) mm 3vs. (1.7±0.2) mm 3, t=2.674, P=0.009; (6.9±0.8) mm 3vs. (7.4±1.0) mm 3, t=2.187, P=0.031; (6.9±0.8) mm 3vs. (7.4±0.9) mm 3, t=2.252, P=0.024]. The differences of gray matter, white matter volume between the two groups showed a similar trend but did not reach statistical significance. And lacunar infarction and cerebral microbleeds were more common in IDH group. The daily living ability scores of the two groups were similar (65.51±11.52 vs. 65.71±11.53, Z=-0.456, P=0.648). The proportion of patients with cognitive abnormalities was higher in the IDH group, without statistical significance. The proportion of depression was similar. Univariate linear regression analysis showed that IDH was significantly negatively correlated with the volume of amygdala, cuneiform cortex, and posterior cingulate gyrus, which control emotions in the brain ( B=-0.117, 95% CI -0.203--0.030, P=0.009; B=-0.484, 95% CI -0.923--0.046, P=0.031; B=-0.485, 95% CI -0.911--0.058, P=0.026). After multivariate adjustment, decreased amygdala volume was still correlated with IDH ( B=-0.111, 95% CI -0.198--0.025, P=0.026). Conclusion:Recurrent IDH may lead to atrophy of various brain components, which may be one of the reasons for cognitive and emotional changes in maintenance hemodialysis patients.
8.Comparison of digital PCR platforms using the molecular marker
Cherl-Joon LEE ; Wonseok SHIN ; Minsik SONG ; Seung-Shick SHIN ; Yujun PARK ; Kornsorn SRIKULNATH ; Dong Hee KIM ; Kyudong HAN
Genomics & Informatics 2023;21(2):e24-
Assays of clinical diagnosis and species identification using molecular markers are performed according to a quantitative method in consideration of sensitivity, cost, speed, convenience, and specificity. However, typical polymerase chain reaction (PCR) assay is difficult to quantify and have various limitations. In addition, to perform quantitative analysis with the quantitative real-time PCR (qRT-PCR) equipment, a standard curve or normalization using reference genes is essential. Within the last a decade, previous studies have reported that the digital PCR (dPCR) assay, a third-generation PCR, can be applied in various fields by overcoming the shortcomings of typical PCR and qRT-PCR assays. We selected Stilla Naica System (Stilla Technologies), Droplet Digital PCR Technology (Bio-Rad), and Lab on an Array Digital Real-Time PCR analyzer system (OPTOLANE) for comparative analysis among the various droplet digital PCR platforms currently in use commercially. Our previous study discovered a molecular marker that can distinguish Hanwoo species (Korean native cattle) using Hanwoo-specific genomic structural variation. Here, we report the pros and cons of the operation of each dPCR platform from various perspectives using this species identification marker. In conclusion, we hope that this study will help researchers to select suitable dPCR platforms according to their purpose and resources.
9.Progress in the relationship between head and neck squamous cell carcinom and the microbial community.
Chenyang LIU ; Yujun LI ; Zhen DONG ; Sen ZHANG ; Hui HUANGFU ; Yue HAN ; Miao CHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(6):498-502
Microorganisms are one of the important factors which maintain the homeostasis of human health. Despite recent advances, the relationship between microorganisms and head and neck squamous cell carcinoma (HNSCC) is still unclear, and the impact of microorganisms on the incidence and prognosis of HNSCC cannot be neglected. Therefore, this article provides a systematic and comprehensive review summarizing the epidemiological evidence of microbial dysbiosis related to HNSCC and discusses the associations between them.
Humans
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Carcinoma, Squamous Cell/pathology*
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Epithelial Cells
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Head and Neck Neoplasms
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Microbiota
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Prognosis
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Squamous Cell Carcinoma of Head and Neck
10.PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2023;13(1):157-173
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

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