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.Epidemiological characteristics and influencing factors of the cluster outbreaks of influenza-like illness in Yangpu District, Shanghai, 2012‒2022
Qianru XIE ; Chenyan JIANG ; Fangfang TAO ; Peng QIAO
Shanghai Journal of Preventive Medicine 2025;37(4):319-323
ObjectiveTo analyze the epidemiological characteristics and influencing factors of clustered influenza-like illness (ILI) outbreaks in Yangpu District, Shanghai from 2012 to 2022, and to provide a scientific basis for formulating specific prevention and control measures of influenza in this district. MethodsData on clustered ILI outbreaks from 2012 to 2022 were collected, and the epidemiological pattern of the cluster outbreaks of influenza and its influencing factors of prevalence and duration were explored using statistical methods such as descriptive epidemiology, χ² test and logistic regression analysis. ResultsA total of 60 clustered ILI outbreaks were reported in Yangpu District, Shanghai from 2012 to 2022, with a cumulative number of 543 cases and an annual average incidence rate of 16.96%. The male-to-female ratio was1.06∶1. The largest number of ILI were reported in 2019, mainly from November to January of the next year, with December being the peak of outbreaks. The Streets of Changhai Rd. in Yangpu District had the largest number of reported outbreaks, accounting for 30.00% of the total outbreaks. Influenza cluster outbreaks occurred in schools, with the majority of outbreaks and cases reported in primary schools (accounting for 65.00% and 62.06% of the total, respectively). The outbreaks were mainly caused by influenza B virus, accounting for 50% of the total number of outbreaks. The prevalence rate of influenza cluster outbreaks varied among different schools in terms of their affiliated streets, school attributes and school types, with those in Kongjiang Rd. Subdistrict, private schools, and childcare institutions being relatively high. The duration of outbreaks reported for >2 days was longer than those reported for ≤2 days (OR=8.604, 95%CI: 1.509–49.067). ConclusionThe ILI outbreaks in Yangpu District present a seasonal pattern, with primary schools and Changhai Rd. Street as the targeted places for implementing prevention and control measures. Timely detection and reporting and active disposal can prevent a further spread of the outbreaks.
3.Establishment and Implementation of Post-marketing Benefit-risk Assessment Strategy for Traditional Chinese Medicine
Meng QIAO ; Wenxi PENG ; Qiang ZHANG ; Chao LEI ; Yanming XIE ; Zhifei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):253-260
The field of post-marketing benefit-risk assessment for traditional Chinese medicine(TCM) is still in its nascent stage, lacking a universally accepted and cohesive evaluation framework and standards. This study presented a strategy developed for the benefit-risk assessment of post-marketing of TCM, and explored the critical techniques and specific implementation steps involved in the assessment process. Initially, appropriate qualitative assessment frameworks and quantitative analysis models were selected for the integrated qualitative and quantitative benefit-risk assessment. Subsequently, key technologies were outlined, including the establishment of a benefit-risk indicator system, the assignment of indicator weights, and the definition of criteria attributes. Furthermore, the implementation steps were elaborated, which involved defining decision-making issues, data collection, evaluation methodologies, variability factors, and sensitivity analysis. Finally, a case study of the benefit-risk assessment of a TCM injection for hepatitis B treatment was conducted to validate the feasibility of the proposed strategy. The objective of this research was to provide theoretical support and practical references for the development of a comprehensive post-marketing benefit-risk assessment system for TCM.
4.Establishment of a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things and blockchain technology
Yanjing MA ; Jun HANG ; Yanan WANG ; Wenting JIANG ; Aiming SHI ; Jie PAN ; Peng QIAO
China Pharmacy 2025;36(20):2502-2506
OBJECTIVE To establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things (IoT) and blockchain technology, and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions: work efficiency, medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation (October to December 2024) and after the system implementation (January to March 2025). RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs, centered around the drug traceability code management system, was successfully established. The acceptance time for incoming drugs was shortened from (4.65±0.26) h before implementation to (0.34±0.08) h after implementation (P< 0.05). The number of collected drug traceability codes increased from 419 018 to 1 236 522, and the coverage rate of traceability codes rose from 28.36% to 89.88% (P<0.05). The time pharmacists spent on drug expiry management per week decreased from (128.40±19.20) min to (0.56±0.13) min (P<0.05), and the dispensing time for a single prescription (excluding a part of injections and repackaged drugs) was reduced from (143.25±17.67) s to (15.24±10.08) s (P<0.05). The time for drug return was reduced from 129.90 (122.32, 137.00) s to 104.36 (89.91, 117.33) s(P<0.05); the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched, there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality, improve pharmacist work efficiency, and reduce drug management risks, thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.
5.Challenges in application of artificial intelligence in healthcare field and response strategies
Zichen YE ; Peng XUE ; Youlin QIAO ; Yu JIANG
Chinese Journal of Epidemiology 2024;45(7):1030-1038
The rapid development of artificial intelligence in the field of healthcare has greatly improved diagnosis accuracy, disease prediction, personalized treatment and healthcare resource management. However, with the widespread application of medical artificial intelligence, challenges has emerged in the aspects of medical data, model development and evaluation, and societal considerations. Therefore, this study aims to explore challenges in the application of artificial intelligence in healthcare and suggest a series of feasible solutions to improve medical professional and researchers' understanding of medical artificial intelligence and enhance the quality of healthcare in clinical practice
6.Study on the direct economic burden and relevant influencing factors of 233 multidrug/rifampicin-resistant pulmonary tuberculosis patients in Jiangsu Province
Hui DING ; Peng LU ; Xiaoyan DING ; Zhongqi LI ; Limei ZHU ; Qiao LIU
Chinese Journal of Epidemiology 2024;45(9):1251-1257
Objective:To explore the direct economic burden and factors affecting out-of-pocket direct costs of multidrug-/rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB) patients in Jiangsu Province.Methods:MDR/RR-PTB patients diagnosed and treated at 13 municipal tuberculosis (TB)-designated hospitals in Jiangsu Province between January 1, 2021, and December 31, 2022, were included, and basic information and direct economic costs were obtained through questionnaires and hospital information systems. Stepwise multiple linear regression was used to analyze the factors influencing patients' out-of-pocket direct costs.Results:The age of the 233 MDR/RR-PTB patients was (44.04±15.64) years. The M( Q1, Q3) direct medical expense of the patients was 134 051.00 (98 934.01,163 205.73) Yuan, of which the M( Q1, Q3) reimbursement by health insurance or policy reduction was 100 462.10 (78 120.00,130 816.00) Yuan, and the M( Q1, Q3) out-of-pocket direct medical expense was 21 694.62 (14 734.83,37 813.00) Yuan. The M( Q1, Q3) direct non-medical expense was 4 971.00 (3 138.00,7 870.00) Yuan. Age, registered residence location, TB resulting in divorce or separation from spouse or partner, drug resistance test results, and treatment regimens were the influencing factors associated with out-of-pocket direct costs for MDR/RR-PTB patients. Conclusions:The direct economic burden caused by MDR/RR-PTB in Jiangsu Province is heavy. It is necessary to emphasize psychological guidance and care for MDR/RR-PTB patients, improve the diagnosis, treatment, and management of MDR/RR-PTB, and effectively reduce the economic burden of MDR/RR-PTB patients.
7.Construction of enteral nutrition nursing scheme for patients with abdominal hypertension in ICU based on intra-abdominal pressure classification
Meimei WANG ; Anhua QIAO ; Yin′e WANG ; Bingmei ZHOU ; Wenfang LI ; Fei PENG
Chinese Journal of Practical Nursing 2024;40(15):1133-1141
Objective:To construct the enteral nutrition nursing scheme of ICU patients with abdominal hypertension based on internal abdominal pressure classification, and provide reference for effectively preventing enteral nutrition intolerance of ICU patients with abdominal hypertension.Methods:According to the "6S" evidence pyramid model, searched from top to bottom for relevant literature on enteral nutrition support for ICU patients with abdominal hypertension in databases such as BMJ Best Practice, Cochrane Library, Guidelines International Network, Medlive, UpToDate, PubMed, Ovid, Web of Science, Embase, China National Knowledge Infrastructure, VIP, Wanfang Medicine, Chinese Biomedical Literature. Developed an enteral nutrition care plan for ICU patients with abdominal hypertension based on intra-abdominal pressure grading, with a search date from database establishment to January 25, 2023. The Delphi expert letter consultation method was used to conduct two rounds of letter consultation with 20 experts to solicit expert opinions and determine the intervention plan.Results:The age of 20 experts was (43.75 ± 5.28) years old, with a working experience of (22.00 ± 6.98) years. The effective recovery rates of the two rounds of Delphi expert correspondence questionnaires were 100%(20/20), the expert judgment basis coefficients were 0.945 and 0.970, the familiarity coefficients were 0.865 and 0.895, and the authority coefficients were 0.905 and 0.932, respectively. Kendall coordination coefficient of importance of the first, second and third level items in the two rounds of expert correspondence were 0.100, 0.093, 0.098 and 0.200, 0.165, 0.119. The Kendall coordination coefficients of operability for the first, second and third level items were 0.117, 0.130, 0.115 and 0.200, 0.184, 0.154, respectively. Finally, an enteral nutrition nursing scheme for patients with abdominal hypertension in ICU was formed, which included 5 primary items, 30 secondary items and 51 tertiary items.Conclusions:The Delphi method in this study has a high degree of authority and enthusiasm of experts, and a good degree of coordination of expert opinions. The established enteral nutrition nursing scheme for ICU patients with abdominal hypertension based on intra-abdominal pressure classification is reliable and scientific, and can provide reference for clinical nursing practice of enteral nutrition for ICU patients with abdominal hypertension.
8.Development of biological safety protection third-level laboratory based on folding-modular shelters
Si-Qing ZHAO ; Jian-Qiao XIA ; Zhong-Jie SUN ; Kang OUYANG ; Xiao-Jun JIN ; Kang-Li ZHOU ; Wei XIE ; Hai-Yang LI ; Da-Peng JIANG ; Yan-Yan GAO ; Bei SUN
Chinese Medical Equipment Journal 2024;45(3):41-46
Objective To develop a biological safety protection third-level(BSL-3)laboratory based on folding-modular shelters to solve the problems of the existing laboratories in space and function expansion,large-scale deployment and low-cost transportation.Methods The BSL-3 laboratory was composed of a folding combined shelter module,a ventilation and purification module,a power supply and distribution module,a monitoring and communication module,a control system module and an equipment module.The folding combined shelter module used a leveling base frame as the foundation and a lightweight panel as the enclosure mechanism,and was divided into an auxiliary area and a protection protected area;the ventilation and purification module was made up of an air supply unit and an air exhaust unit,the air supply unit was integrated with a fresh-air air conditioner and the exhaust unit was equipped with a main fan,a standby fan and a bag in/bag out filter;the control system module adopted a supervision mode of decentralized control and centralized management,which executed communication with the data server as the center and Profinet protocol and MODBUS-TCP.Results The BSL-3 laboratory proved to meet the requirements of relevant standards in internal microenvironment,airflow direction,airtightness,working condition and disinfection effect.Conclusion The BSL-3 laboratory is compatible with large-scale transport and deployment and facilitates reliable and safe experiments for epidemic prevention and control and cross-regional support.[Chinese Medical Equipment Journal,2024,45(3):41-46]
9.Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis:Possible through SIRT3-AMPK axis
Han XIN ; Ning YAN ; Dou XINYUE ; Wang YIWEN ; Shan QIYUAN ; Shi KAO ; Wang ZEPING ; Ding CHUAN ; Hao MIN ; Wang KUILONG ; Peng MENGYUN ; Kuang HAODAN ; Yang QIAO ; Sang XIANAN ; Cao GANG
Journal of Pharmaceutical Analysis 2024;14(5):758-771
Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.
10.Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis
Bao YINI ; Shan QIYUAN ; Lu KEDA ; Yang QIAO ; Liang YING ; Kuang HAODAN ; Wang LU ; Hao MIN ; Peng MENGYUN ; Zhang SHUOSHENG ; Cao GANG
Journal of Pharmaceutical Analysis 2024;14(8):1099-1109
Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibro-blast activation,and immune cell recruitment.In this review,we summarize recent advances in un-derstanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.

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