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.Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).
Qing ZHAO ; Tong WANG ; Hongbin WANG ; Peng CAO ; Chengyu JIANG ; Hongzhi QIAO ; Lihua PENG ; Xingdong LIN ; Yunyao JIANG ; Honglei JIN ; Huantian ZHANG ; Shengpeng WANG ; Yang WANG ; Ying WANG ; Xi CHEN ; Junbing FAN ; Bo LI ; Geng LI ; Bifeng LIU ; Zhiyang LI ; Suhua QI ; Mingzhen ZHANG ; Jianjian ZHENG ; Jiuyao ZHOU ; Lei ZHENG ; Kewei ZHAO
Chinese Herbal Medicines 2024;16(1):3-12
To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.
6.Meta-analysis of the myopia control effect of orthokeratology lenses with dif-ferent back optical zone diameters
Wenting WANG ; Lu QIAO ; Lemin CHEN ; Shaomin PENG
Recent Advances in Ophthalmology 2024;44(4):311-316
Objective To systematically evaluate the changes in axial length and treatment zone diameter among my-opic patients wearing orthokeratology lenses with different back optic zone diameters.Methods A comprehensive litera-ture search was conducted on PubMed,Embase,the Cochrane Library,Web of Science,Wangfang Med Online and CNKI databases in both Chinese and English to identify randomized controlled trials or controlled trials investigating orthokeratol-ogy lenses with varying back optical zone diameters.The literature was thoroughly reviewed by two researchers,who ex-tracted relevant data and conducted a methodological quality evaluation.Finally,meta-analysis was performed using Rev-Man 5.3 software.In all the included studies,orthokeratology lenses with a conventional back optic zone diameter were taken as the control group,while orthokeratology lenses with a reduced back optic zone diameter were utilized as the ex-perimental group.Results Eight studies involving 437 patients(459 eyes)with myopia were included.The results of me-ta-analysis showed that the axial length changes in the experimental group were significantly lower than those of the control group after wearing orthokeratology lenses for 6 months and 12 months(6 months:MD=-0.09,95%CI:-0.10 to-0.07,Z=10.50,P<0.05;12 months:MD=-0.11,95%CI:-0.13 to-0.09,Z=12.19,P<0.05);significant differ-ences in treatment zone diameter were observed between the experimental and control groups at various time points follow-ing orthokeratology lens wearing(MD=-0.82,95%CI:-1.04 to-0.59,Z=7.03,P<0.05).Conclusion Orthoker-atology lenses designed with smaller back optical zone diameters can effectively delay axial length growth in myopic pa-tients,but their long-term efficacy needs to be confirmed.
7.Application of miniprobe endoscopic ultrasound in endoscopic surgery of small-diameter and low-grade rectum neuroendocrine neoplasm
Jian-Jun LI ; Chao-Qiang FAN ; Xin YANG ; Xue PENG ; Hao LIN ; Xu-Biao NIE ; Shi-Ming YANG ; Qiu-Jian QIAO ; Jian-Ying BAI
Journal of Regional Anatomy and Operative Surgery 2024;33(1):59-62
Objective To evaluate the value of miniprobe endoscopic ultrasound(EUS)in guiding endoscopic treatment of small-diameter(maximum diameter less than 1 cm)and low-grade(G1 grade)rectum neuroendocrine neoplasm(R-NEN),and to provide evidence and clues for its clinical application and further research.Methods The clinical data of 85 cases of low-grade(G1 grade)R-NEN with a maximum diameter of less than 1 cm who underwent endoscopic treatment in our center from January 2014 to December 2020 were retrospectively analyzed.The patients were divided into the EUS group(37 cases)and control group(48 cases)according to whether EUS was performed before endoscopic treatment.The positive rate of incision margin,the incidence of complications,the recurrence rate,the hospital stay,the cost of hospitalization and endoscopic therapy were compared between the two groups.Results The positive rate of incision margin in the EUS group was significantly lower than that in control group(P<0.05).There was no significant difference in the incidence of complications,tumor recurrence rate,hospital stay or hospital costs between the two groups(P>0.05).There was statistically significant difference in the endoscopic therapy between the two groups(P<0.05).Conclusion Evaluating the lesion depth of small-diameter and low-grade(G1 grade)R-NEN before surgery by miniprobe EUS and selecting endoscopic surgery according to its results of can significantly reduce the residual risk of resection margin tumors.
8.The current situation of willingness to receive prophylactic treatment among students with latent tuberculosis infection and its influencing factors in Jiangsu Province
WANG Zhan ; LI Zhongqi ; DING Xiaoyan ; LU Peng ; ZHU Limei ; LIU Qiao ; LU Wei
China Tropical Medicine 2024;24(3):244-
Objective To assess the willingness of students with latent tuberculosis infection (LTBI) in Jiangsu Province to undergo preventive treatment and identify factors influencing their decision, aiming to provide insights for tuberculosis prevention and control strategies in school. Methods The physical examination information of tuberculosis latent infection cases was collected from screenings of new school enrollment and contacts of tuberculosis patients in 6 cities of Jiangsu Province from December 2022 to December 2023. Data on past medical history and understanding of preventive treatment were gathered through an online questionnaire survey on the website of Juanxing, and the influencing factors related to the willingness to take preventive medication were analyzed by logistic regression analysis model. Results In December 2022 to December 2023, a total of 13 school tuberculosis outbreaks occurred in 6 cities, and 1 661 contacts were screened, among which 162 cases met the criteria for prophylactic medication, 96 cases were included in the study by filling in the questionnaire. A total of 22 600 new students from 56 schools participated in the TB screening upon enrollment, of which 358 tested positive for the tuberculin skin test alone, meeting the criteria for preventive medication, and 251 of them completed the willingness survey. Finally, 347 students who met the criteria for preventive treatment were included in the study, with 164 expressing to accept preventive treatment representing a treatment acceptance rate of 47.3%. The results of multivariate analysis showed that university (OR=17.950, 95%CI: 3.078-104.686, P=0.001) and contact with the source of school tuberculosis epidemic (OR=19.542, 95%CI: 6.289-60.726, P<0.001) were associated with increased willingness to receive preventive treatment, while unclear whether to pay for the drugs themselves (OR=0.349, 95%CI:0.133-0.916, P=0.032) was associated with decreased willingness to receive preventive treatment. Compared with Huai'an City, the willingness to receive preventive treatment was significantly lower among students from Nantong City (OR=0.005, 95%CI:0.000-0.063, P<0.001), Nanjing City (OR=0.022, 95%CI: 0.003-0.703, P<0.001) and Lianyungang City (OR=0.074, 95%CI:0.008-0.703, P=0.023). Conclusions The acceptance rate of preventive treatment among LTBI students in Jiangsu Province is not high and is affected by multiple factors. Health education and medication mobilization for preventive medication are essential.
9.Network Correlation Analysis Between Components of Shuanghuanglian Injection and Allergy-like Targets
Weilong ZHANG ; Hong HE ; Ru QIAO ; Peng HE ; Wenjiao LI ; Liangqi ZHANG ; Xiaoxuan LIU ; Siqi HUANG ; Xue PAN ; Fuyuan HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):190-197
ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine(TCM) compounds, a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection(SHLI), in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI. MethodAfter one week of adaptive feeding, 72 SPF-grade SD male rats were randomly divided into blank group, SHLI standard group, Lonicerae Japonicae Flos(LJF) group, Scutellariae Radix(SR) group, Forsythiae Fructus(FF) group, and 7 groups of SHLI matching groups(groups 1-7), with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state, high performance liquid chromatography(HPLC) characterization profiles of the testing drugs and plasma components in each group were established, and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay(ELISA) was used to determine the changes of immunoglobulin E(IgE), histamine(HIS), tryptase(TPS), total complement(CH50) and terminal complement complex(C5b-9) in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets, and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values. ResultELISA results showed that, compared with the blank group, groups 1-3 could significantly increase the IgE level, groups 1-2, groups 4-6 and SHLI standard group could significantly increase the HIS level, group 4 could significantly increase the CH50 level, groups 1, 3-4, LJF group and FF group could significantly increase the TPS level, SR group could significantly increase the C5b-9 level, and the differences were all statistically significant(P<0.05). According to the retention time of chromatographic peaks, it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2, indicating that C6 had the greatest effect on the allergic reaction, and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS, indicating that component group C2 had the greatest contribution to the whole network. ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network, this study clarified that component group C6 may be a potential allergen in SHLI, and the component group C2 may be a key node in the mechanism of drug action, which can provide new strategies and methods for the screening of allergens in TCM injections.
10.Theory and Analysis of Pharmacokinetic and Chromatokinetics Dose-time Characterization Methods in Traditional Chinese Medicine
Ru QIAO ; Peng HE ; Qijun HE ; Haiying LI ; Meifeng XIAO ; Kaiwen DENG ; Fuyuan HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):178-186
ObjectiveTo establish a theoretical system of pharmacokinetic and spectrokinetic dose-time characterization of traditional Chinese medicine(TCM). By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos, Houttuyniae Herba injection, Lonicerae Japonicae Flosand Buyang Huanwutang, this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship, namely half-life, statistical moment and statistics, in order to find the most suitable method for characterizing the relationship. MethodTen mice were randomly selected from 100 Kunming mice as the blank group, and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling. After successful modeling, the mice were gavaged with aqueous extract of Lonicerae Flos(30 g∙kg-1), and the blank group was gavaged with an equal volume of normal saline. The plasma of mice was collected at different time points to determine the content changes of components. At the same time, the pharmacokinetic results of Houttuyniae Herba injection, Lonicerae Japonicae Flos and Buyang Huanwutang were included, and the pharmacokinetic and spectrokinetic parameters were calculated. Then the difference in the time of calculating 95% total component content of metabolism by half-life method, statistical moment method and statistical method was compared. ResultOn the basis of the half-life method, the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established. The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied, with cryptochlorogenic acid and rutin showing a two-compartment model and the other components showing a one-compartment model. After calculation of spectrokinetic similarity, the metabolic patterns among the components contained in Houttuyniae Herba injection, Lonicerae Japonicae Flos, Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo. The time to metabolize 95% of the total components of the four research subjects in vivo was calculated by the half-life method, statistical moment method and statistical method, and it was found that the difference between statistical moment method and half-life method was large, and the difference between statistical moment method and statistical method was small. ConclusionStatistical method not only reflects the characteristics of statistical moment method, characterizes the dispersion degree of each component, but also can be associated with fingerprint to form spectrokinetics, characterizing the dose-time relationship of 95% of drug components, which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.

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