1.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
2.Construction of a predictive model for poorly differentiated adenocarcinoma in pulmonary nodules using CT combined with tumor markers
Jie JIANG ; Feng LIU ; Bo WANG ; Qin WANG ; Jian ZHONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):73-79
Objective To establish and internally validate a predictive model for poorly differentiated adenocarcinoma based on CT imaging and tumor marker results. Methods Patients with solid and partially solid lung nodules who underwent lung nodule surgery at the Department of Thoracic Surgery, the Affiliated Brain Hospital of Nanjing Medical University in 2023 were selected and randomly divided into a training set and a validation set at a ratio of 7:3. Patients' CT features, including average density value, maximum diameter, pleural indentation sign, and bronchial inflation sign, as well as patient tumor marker results, were collected. Based on postoperative pathological results, patients were divided into a poorly differentiated adenocarcinoma group and a non-poorly differentiated adenocarcinoma group. Univariate analysis and logistic regression analysis were performed on the training set to establish the predictive model. The receiver operating characteristic (ROC) curve was used to evaluate the model's discriminability, the calibration curve to assess the model's consistency, and the decision curve to evaluate the clinical value of the model, which was then validated in the validation set. Results A total of 299 patients were included, with 103 males and 196 females, with a median age of 57.00 (51.00, 67.25) years. There were 211 patients in the training set and 88 patients in the validation set. Multivariate analysis showed that carcinoembryonic antigen (CEA) value [OR=1.476, 95%CI (1.184, 1.983), P=0.002], cytokeratin 19 fragment antigen (CYFRA21-1) value [OR=1.388, 95%CI (1.084, 1.993), P=0.035], maximum tumor diameter [OR=6.233, 95%CI (1.069, 15.415), P=0.017], and average density [OR=1.083, 95%CI (1.020, 1.194), P=0.040] were independent risk factors for solid and partially solid lung nodules as poorly differentiated adenocarcinoma. Based on this, a predictive model was constructed with an area under the ROC curve of 0.896 [95%CI (0.810, 0.982)], a maximum Youden index corresponding cut-off value of 0.103, sensitivity of 0.750, and specificity of 0.936. Using the Bootstrap method for 1000 samplings, the calibration curve predicted probability was consistent with actual risk. Decision curve analysis indicated positive benefits across all prediction probabilities, demonstrating good clinical value. Conclusion For patients with solid and partially solid lung nodules, preoperative use of CT to measure tumor average density value and maximum diameter, combined with tumor markers CEA and CYFRA21-1 values, can effectively predict whether it is poorly differentiated adenocarcinoma, allowing for early intervention.
3.Ethical issues and reflections on clinical research of radiopharmaceuticals
Yonglan HU ; Li WANG ; Feng JIANG ; Jiyin ZHOU ; Zhengjun CHEN ; Jie ZHANG ; Zengrui ZHANG
Chinese Medical Ethics 2025;38(2):254-260
Radiopharmaceuticals play an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases, malignant tumors, central nervous system diseases, and other diseases. Under the urgent need for clinical diagnosis and treatment as well as medical development, the clinical research of radiopharmaceuticals has become a hotspot in international research. By analyzing the current situation of clinical research on radiopharmaceuticals in Europe, America, and China, the ethical issues of clinical research on radiopharmaceuticals were elaborated from four aspects, including lack of relevant laws and regulations, a higher risk of radiopharmaceuticals, dilemmas in ethical review, and insufficient radiation protection. Response principles and measures were proposed from four aspects, including improving regulations and policies, enhancing radiological protection for all parties involved in the research, strengthening ethical review, and reinforcing the training of relevant personnel, to enhance the quality and level of clinical research on radiopharmaceuticals.
4.The Mechanisms of Quercetin in Improving Alzheimer’s Disease
Yu-Meng ZHANG ; Yu-Shan TIAN ; Jie LI ; Wen-Jun MU ; Chang-Feng YIN ; Huan CHEN ; Hong-Wei HOU
Progress in Biochemistry and Biophysics 2025;52(2):334-347
Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.
5.Research advances in the effects of orexin and its receptor-related drugs on depression
Zhaoshu JIANG ; Ming CHENG ; Jie YANG ; Feng CAO ; Zhen ZHANG
China Pharmacy 2025;36(4):496-500
Depression is a psychiatric disorder whose main symptoms include low mood, loss of interest, anxiety, sleep disturbances, and changes in appetite. Orexin, a neuropeptide located in hypothalamic neurons, has a wide range of projections throughout the central nervous system and is involved in various behavioral modulations related to depression. This study systematically reviewed the effects of orexin and its receptor-related drugs on depression and found that orexin could exert complex regulatory effects on multiple brain regions by binding to related receptors, affecting emotions, sleep, anxiety, etc. The abnormal state of expression of plasma orexin in patients with depression was found. Exogenous orexin-A, selective orexin receptor 1 antagonists (SORA1s), selective orexin receptor 2 antagonists (SORA2s), and dual orexin receptor antagonists (DORAs) have demonstrated antidepressant-like effects in various animal models of depression. Among them, clinical trials involving exogenous orexin-A are relatively scarce. Drugs related to SORA1s and SORA2s, such as JNJ-61393215 and Setorexant, have made significant progress in the treatment of depression. DORAs, such as Suvorexant, Lemborexant, and Daridorexant, are primarily used to treat insomnia. Notably, Suvorexant has also shown potential in alleviating symptoms of anxiety and depression.
6.Analysis of ancient medical physicians′ spatial theory from the perspective of liver and mingmen visceral manifestation
Chongcheng XI ; Jie ZHANG ; Wenjun WU ; Zhiwen ZHANG ; Shuangqing ZHAI ; Quansheng FENG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):187-192
Yin-yang, visceral manifestation, and ti-yong theories are the core theories of traditional Chinese medicine (TCM) and play a crucial role in its formation and development. With the continuous evolution of Chinese philosophy, TCM philosophy and theories have undergone significant influence, resulting in differing interpretations of the visceral manifestation of liver and mingmen across various historical periods by different medical practitioners. This paper focuses on the different understandings of the position of liver and mingmen, combining relevant philosophical images and TCM anatomical illustrations to deeply explore ancient medical theorists′ concepts regarding the four spatial directions of left, right, up, and down. The research reveals that ancient medical theorists′ conceptualization of spatial theory transitioned from an initial circular motion to a vertical movement, with the focus shifting from the upper part to the lower part. The primary reasons for these differences and changes could be explained by the varying emphasis on the ti-yong theory and differing focal points within the yin-yang theory. This study systematically examines the evolution of visceral manifestation theories related to liver and mingmen, highlights the shifts in physicians′ perspectives on spatial theory, and analyzes the influence of the ti-yong theory and yin-yang theory on these changes. The findings aim to provide a theoretical guide for advancing research and clinical application of spatial theory in TCM, thereby fostering the integration of TCM philosophy with medical theory.
7.The application strategies of non-uniform sampling in the structure elucidation of small molecule compounds—an instantiation using fuziline
Li-li ZHANG ; Ke ZHANG ; Jie LIU ; Chun-wang MENG ; Rui FENG ; Liang XIONG
Acta Pharmaceutica Sinica 2025;60(1):218-224
Two-dimensional nuclear magnetic resonance (2D NMR) is a widely used technique for structural analysis of small molecular compounds. It can obtain information about the hydrogen-hydrogen correlation, hydrogen-carbon single bond correlation, hydrogen-carbon remote correlation, and hydrogen-hydrogen spatial arrangement of compounds. Thus, 2D NMR has an irreplaceable role in the structure elucidation of small molecular products. However, the sample amount of trace components in phytochemical research is very low, and the traditional sampling method (uniform sampling) has problems of poor spectral quality and too long measure time. Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum, which in turn causes strain on the NMR machine. The non-uniform sampling (NUS) technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data, which greatly improves the efficiency of 2D NMR acquisition. In this paper, fuziline, a small molecular compound in the lateral roots of
8.Status of Clinical Practice Guideline Information Platforms
Xueqin ZHANG ; Yun ZHAO ; Jie LIU ; Long GE ; Ying XING ; Simeng REN ; Yifei WANG ; Wenzheng ZHANG ; Di ZHANG ; Shihua WANG ; Yao SUN ; Min WU ; Lin FENG ; Tiancai WEN
Medical Journal of Peking Union Medical College Hospital 2025;16(2):462-471
Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.
9.Terms Related to The Study of Biomacromolecular Condensates
Ke RUAN ; Xiao-Feng FANG ; Dan LI ; Pi-Long LI ; Yi LIN ; Zheng WANG ; Yun-Yu SHI ; Ming-Jie ZHANG ; Hong ZHANG ; Cong LIU
Progress in Biochemistry and Biophysics 2025;52(4):1027-1035
Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.
10.Analysis of radiosensitivity indicators for radiation workers at a nuclear power plant
Nan MA ; Junchao FENG ; Yulong LIU ; Jie LI ; Yu GAO
Chinese Journal of Radiological Health 2025;34(2):264-269
Objective To analyze the health effects of long-term occupational exposure to ionizing radiation on radiation workers in a nuclear power plant, and to provide a scientific basis for their occupational health monitoring. Methods In 2023, 183 radiation workers in a nuclear power plant were subjected to the analysis of blood cell parameters such as mean red blood cell count, white blood cell count (WBC), lymphocyte count, and hemoglobin count, thyroid function indicators such as serum triiodothyronine, thyroxine, and thyrotropin, as well as the chromosomal aberration rate and micronucleus rate of the lymphocytes in the peripheral blood. Results The blood cell parameters, thyroid function indicators, chromosomal aberration rate, and micronucleus rate of these radiation workers in the nuclear power plant were within normal reference ranges. Comparison among radiation workers with different ages showed statistically significant differences in triiodothyronine (H = 6.98, P < 0.05) and micronucleus rate (H = 48.44, P < 0.05). Among the three groups of radiation workers with different working years, WBC was significantly different (χ2 = 3.87, P < 0.05), with the lowest WBC observed in radiation workers with ≥ 20 years of service. Thyroxine (χ2 = 4.01, P < 0.05) and micronucleus rate (H = 40.95, P < 0.05) also varied significantly among these three groups. Conclusion Thyroid triiodothyronine level and micronucleus rate were affected by age, while WBC, thyroid thyroxine level, and micronucleus rate were related to working years. Targeted health management should be carried out for radiation workers in nuclear power plants to improve the awareness of radiation protection and continuously enhance their health status.


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