1.Application of CRISPR/Cas System in Precision Medicine for Triple-negative Breast Cancer
Hui-Ling LIN ; Yu-Xin OUYANG ; Wan-Ying TANG ; Mi HU ; Mao PENG ; Ping-Ping HE ; Xin-Ping OUYANG
Progress in Biochemistry and Biophysics 2025;52(2):279-289
Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.
2.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
3.Cloning, subcellular localization and expression analysis of SmIAA7 gene from Salvia miltiorrhiza
Yu-ying HUANG ; Ying CHEN ; Bao-wei WANG ; Fan-yuan GUAN ; Yu-yan ZHENG ; Jing FAN ; Jin-ling WANG ; Xiu-hua HU ; Xiao-hui WANG
Acta Pharmaceutica Sinica 2025;60(2):514-525
The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified
4.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.
5.Pharmacokinetics and bioequivalence study of teriflunomide tablets in healthy Chinese subjects
Li-Li LIN ; Yan JIANG ; Qin ZHANG ; Hui-Ling QIN ; Qian ZHANG ; Yang XU ; Wei LIANG ; Lin-Ying MENG ; Zhao-Xing CHU ; Wei HU
The Chinese Journal of Clinical Pharmacology 2024;40(3):425-429
Objective To compare the pharmacokinetic profiles of the two teriflunomide tablets in healthy Chinese subjects under fasting and fed conditions and to evaluate their bioequivalence and safety.Methods A randomized,open,single-dose,parallel trial design was used to enroll 31 and 32 healthy Chinese male subjects in the fasting and fed groups,who were randomized to a single oral dose of 14 mg of either reference or test preparation of teriflunomide tablets.The plasma concentrations of teriflunomide were determined using liquid chromatography-tandem mass spectrometry method,and Phoenix WinNonlin 8.1 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of teriflunomide.The main pharmacokinetic parameters of teriflunomide in the fasting group were as follows:Cmax were(2.14±0.27)and(2.27±0.33)μg·mL-1,AUC0-72h were(105.70±11.20)and(107.72±11.77)μg·mL-1·h,tmax was 1.49 and 0.99 h;the main pharmacokinetic parameters of teriflunomide in the fed group were as follows:Cmaxwere(1.83±0.17)and(1.75±0.22)μg·mL-1,AUC0-72h were(102.66±9.18)and(101.57±13.01)μg·mL-1·h,tmax was 4.01 and 4.99 h.The 90%confidence intervals for the geometric means of Cmax and AUC0-72h for reference and test preparations in the fasting and fed groups were in the range of 80%to 125%.Conclusion The pharmacokinetic characteristics of the 2 formulations were similar under fasting and fed administration conditions,with good bioequivalence and safety;Postprandial administration may delay the time to peak of the drug.
6.Identification and quality evaluation of germplasm resources of commercial Acanthopanax senticosus based on DNA barcodes and HPLC
Shan-hu LIU ; Zhi-fei ZHANG ; Yu-ying HUANG ; Zi-qi LIU ; Wen-qin CHEN ; La-ha AMU ; Xin WANG ; Yue SHI ; Xiao-qin ZHANG ; Gao-jie HE ; Ke-lu AN ; Xiao-hui WANG ; Sheng-li WEI
Acta Pharmaceutica Sinica 2024;59(7):2171-2178
italic>Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial
7.Studies on the chemical composition of Ferula feruloides
Ying-he BI ; Ke-jian PANG ; Hui-zi LI ; Yerlan BAHETJAN ; Muguli MUHAXI ; Yan HU ; Xin-zhou YANG
Acta Pharmaceutica Sinica 2024;59(7):2069-2076
Eleven compounds were isolated and purified from the ethyl acetate part of 80% ethanol extract of
8.Guiding recommendations for fertility preservation of female patients of reproductive age based on modified Delphi method
Ming-Xia LI ; Shu-Hui HU ; Shu-Yi SHAO ; Ying ZHANG
Fudan University Journal of Medical Sciences 2024;51(2):151-158,165
Objective To obtain guiding recommendations for the development of fertility preservation in female patients of reproductive age,so as to promote the scientific,standardized and orderly implementation of fertility preservation work.Methods A previous questionnaire survey was used to determine the preliminary recommendations,a modified Delphi method was used to invite 18 domestic experts of fertility preservation to conduct two rounds of expert consultation.Then we adjusted and summarized recommendations according to the results of the consultation.Results Finally,14 guiding recommendations for the development of fertility preservation in female patients of reproductive age were obtained according to the results of the Delphi consultation,including 5 recommendations at technical level,5 recommendations at political level and 4 recommendations at educational level.At technical level,it was proposed to establish a standardized operation process;at political level,it was proposed to improve the relevant legislation of fertility preservation in China to protect the safety and interests of patients;at educational level,it was suggested to take various forms to promote the mass dissemination of fertility preservation knowledge.Conclusion Guiding recommendations for fertility preservation in female patients of reproductive age can provide detailed and comprehensive guidance for promoting fertility preservation in female patients of reproductive age in Shanghai,and provide reference for carrying out fertility preservation in other regions.
9.Clinical Effectiveness and Safety of Bairui Granules (百蕊颗粒) in Treating Patients with Acute Pharyngitis with Wind-Heat Syndrome: A Multi-Center, Double-Blind, Double-Simulation, Randomized Controlled Trial
Siming LIU ; Hui ZHOU ; Qiang LI ; Min ZHOU ; Qixiang WU ; Shanjun YANG ; Jun WANG ; Jingjing YUAN ; Ying ZHANG ; Ziqi ZHU ; Jingyi HU ; Shuang WU ; Mengting LI ; Zhanfeng YAN
Journal of Traditional Chinese Medicine 2024;65(11):1139-1145
ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules (百蕊颗粒) in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter, double-blind, double-simulation, randomised controlled trial was conducted, in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited, and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group, 108 cases were orally administered with Bairui Granules plus Reyanning Granules (热炎宁颗粒) simulant, and in the control group, 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days, with a follow-up visit on the 6th day. Full analysis set (FAS) analysis and per protocol set (PPS) were used for analysis, respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment; the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment, as well as the visual analogue score (VAS) of sore throat before treatment, every day during the treatment, and follow-up on day 6, and the traditional Chinese medicine (TCM) syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6, and the changes of vital signs, blood routine, urine routine, liver functions, kidney function, the adverse events before and after the treatment were recorded, and safety analysis set (SS) was analysed. Results162 patients entered the FAS and SS analyses, and 158 cases (105 cases in the trial group and 53 cases in the control group) entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% (87/108) in the trial group and 64.81% (35/54) in the control group, and the difference between groups was statistically significant (χ2 = 5.10, P = 0.0239). PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% (84/105) in the trial group and 64.15% (34/53) in the control group, and the difference between groups was statistically significant (χ2 =4.85, P = 0.0277). FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant (P>0.05). Compared with those before treatment, the VAS scores of sore throat were lower in both groups during treatment on day 2, 3, 4, 5, and follow-up on day 6 (P<0.01), but the difference between groups at each time point was not statistically significant (P>0.05). TCM syndrome scores of both groups at the follow-up were lower than that before treatment, and those of the trial group were lower than those of the control group (P<0.01). The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group (P<0.01). There was no significant difference in blood routine, urine routine, liver function, kidney function between groups before and after treatment (P>0.05), and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome, and it could significantly improve the clinical symptoms, accelerate the disappearance time of sore throat with good safety.
10.Assessment of respiratory protection competency of staff in healthcare facilities
Hui-Xue JIA ; Xi YAO ; Mei-Hua HU ; Bing-Li ZHANG ; Xin-Ying SUN ; Zi-Han LI ; Ming-Zhuo DENG ; Lian-He LU ; Jie LI ; Li-Hong SONG ; Jian-Yu LU ; Xue-Mei SONG ; Hang GAO ; Liu-Yi LI
Chinese Journal of Infection Control 2024;23(1):25-31
Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60%participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10%participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

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