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.Human infection with Gongylonema pulchrum: a case report and review of relevant literature during the recent 10 years
Feng TANG ; Xiaofeng SUN ; Xiangzhen XU ; Fanzhen MAO ; Yaobao LIU
Chinese Journal of Schistosomiasis Control 2025;37(3):332-336
This article presents the diagnosis and treatment processes, and morphological and genetic testing of Gongylonema pulchrum in a case with G. pulchrum found in the oral mucosa. In addition, this article reviews publications pertaining to G. pulchrum human infections by Chinese scientists during the recent 10 years and summarizes the demographic and clinical characteristics, location and number of parasites, diagnosis and treatment processes, and epidemiological surveys of cases infected with G. pulchrum, so as to provide insights into improving the diagnostic capability among clinicians.
3.Impact of rigid container material type and loading volume on the sterilization of thoracoscopic instruments
Xue'e FANG ; Yanjun MAO ; Qiuping ZHU ; Yanni CAI ; Jing SHU ; Guifen ZHANG ; Yichun JIN ; Minye TANG ; Ying TAO ; Huiting HU
Shanghai Journal of Preventive Medicine 2025;37(8):697-699
ObjectiveTo explore the impacts of material type and loading volume of rigid containers on the hydrogen peroxide low temperature plasma sterilization of thoracoscopic instruments, to identify the best rigid containers and loading volume of thoracoscopic instruments. MethodsThoracoscopic instruments sterilized by STERRAD® 100NX hydrogen peroxide low temperature plasma in Shanghai Pulmonary Hospital affiliated to Tongji University from August to September 2024 were selected as the research items. According to the material of rigid containers, the instruments were divided into polyethylene case group (A), stainless steel case group (B) and silicone resin case group (C). In terms of the loading volume, the rigid containers were divided into (loading capacity <80%) groups of 8, 10 and 12 instruments. The results of physical monitoring, the first type of chemical indicator card monitoring, and the five types of card luminal chemical process challenge device (PCD) monitoring of the 9 groups of A8, A10, A12, B8, B10, B12, C8, C10 and C12 were compared and evaluated. ResultsCompared to A8, A10 A12, C8, C10 or C12 groups, the thoracoscope instruments in the stainless steel containers in B8, B10 or B12 group had higher hydrogen peroxide concentrations and shorter elapsed time in the pressure check phases 1 and phases 2, with the differences statistically significant (P<0.05), followed by the silicone resin case group and the polyethylene case group. The nine groups of physical parameter monitoring, the first type of chemical indicator monitoring, and the five types of chemical PCD monitoring for lumen sterilization achieved 100% qualification rates, and there were no significant differences in the qualified rates of sterilization among the 9 groups (P>0.05). ConclusionWhen using hydrogen peroxide low temperature plasma to sterilize thoracoscopic instruments, it is recommended to use stainless steel or silicone resin rigid containers with a controlled loading capacity (≤12) to ensure optimal sterilization quality.
4.Development and application of core competency evaluation index system for ethics committee members of drug clinical trial institution
Xiaohua TANG ; Qingqing JIANG ; Haiwei ZHANG ; Weiran MAO ; Yuanyuan YIN ; Jiangdong SUI ; Jun LI ; Xia CHEN
China Pharmacy 2025;36(20):2489-2494
OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution, providing a basis for optimizing the training system for committee members, improving the quality of ethical review, and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation, a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it, ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system, a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide, comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators (ethics and professional knowledge, ethics review ability, communication and expression ability, moral integrity and work style) and 39 secondary indicators (familiarity with the content of clinical trial-related laws and regulations, ability to complete project ethics review and identify ethical defects in research protocols within a short period of time, ability to judge the scientific value of clinical research, etc.). The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge, ethical norms, review efficiency, risk judgment, and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training, qualification certification, and standardized management of ethics committees.
5.Pharmacological Effect of Phellodendri Chinensis Cortex and Active Components on Gout: A Review
Min LI ; Yunyun QUAN ; Ting WANG ; Li LI ; Jin ZENG ; Junning ZHAO ; Jiuzhou MAO ; Yangfan TANG ; Zhujun YIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):286-298
Gout is a metabolic disease closely associated with hyperuricemia and urate deposition. Because of the complex pathogenesis, high morbidity, multiple complications, and increasingly young patients, gout has received worldwide attention. Currently, western medicine mainly treats gout by lowering the uric acid level and reducing inflammation, which, however, causes serious adverse reactions and has contraindications. Phellodendri Chinensis Cortex (PCC) is the dried bark of Phellodendron chinense, with the effects of clearing heat, drying dampness, purging fire, detoxifying, and treating sores. Studies have shown that PCC and its active components have anti-inflammatory, pain-relieving, uric acid-lowering, and anti-gout activities, with extensive sources and high safety. PCC and its active components could prevent and treat gout through multi-targets and multi-pathways, whereas the systematic review remains to be carried out. Therefore, this paper summarized the pharmacological activities and mechanisms of PCC and its active components in the treatment of gout. The available studies have shown that PCC and its active components exert the anti-gout effect by lowering the uric acid level, reducing inflammation, alleviating oxidative stress, and regulationg intestinal flora, and protecting the kidneys. Particularly, the active components represented by alkaloids contribute obviously to the therapeutic effect of of PCC. Herein, we analyzed the problems and future development of the research on PCC, aiming to provide theoretical support and a scientific basis for the research and development of new drugs against gout.
6.Latent profile analysis of return-to-work self-efficacy of postoperative patients with thyroid cancer
Xiaoxia TANG ; Xiaolin YI ; Mei WANG ; Rui CHEN ; Xumin ZHOU ; Huina MAO
Chinese Journal of Practical Nursing 2024;40(11):831-839
Objective:To explore the potential categories of return-to-work self-efficacy of postoperative patients with thyroid cancer and analyze the influencing factors, so as to provide theoretical basis for implementing precise interventions of occupational rehabilitation.Methods:This was a cross-sectional study. A convenient sampling method was used to select 257 postoperative patients with thyroid cancer in Zhujiang Hospital of Southern Medical University from May 2022 to July 2023. The General Information Questionnaire, Return-To-Work Self-Efficacy Questionnaire and Cancer Fatigue Scale were used for investigation. Latent profile analysis was used to explore the potential categories of return-to-work self-efficacy of postoperative patients with thyroid cancer. Logistic regression and decision tree were used to analyze the influencing factors of different potential categories.Results:Finally, 250 postoperative patients with thyroid cancer were included. There were 76 males and 174 females, aged (37.91 ± 8.04) years old. The return-to-work self-efficacy of postoperative patients with thyroid cancer was divided into 2 potential categories: low return-to-work self-efficacy group (72.0%, 180/250) and high return-to-work self-efficacy group (28.0%, 70/250). Logistic regression showed education, thyrotropin suppressive therapy, cancer-related fatigue and age were factors influencing the potential categories of return-to-work self-efficacy of postoperative patients with thyroid cancer ( OR values were 0.951 - 19.820, all P<0.05). Decision tree model showed education level and cancer-related fatigue were the most important factors ( χ2 = 31.40, 16.95, both P<0.05). Conclusions:There were two potential categories of return-to-work self-efficacy of postoperative patients with thyroid cancer. Most of them had low levels of return-to-work self-efficacy. Health care professionals should focus on patients who are less educated and having cancer-related fatigue, meanwhile, should not ignore patients who are substandard thyrotropin suppressive therapy, and older. Implement precise interventions of occupational rehabilitation to improve the return-to-work self-efficacy of postoperative patients with thyroid cancer so as to help them reintegrate into society.
7.miR-146a-3p regulates astrocyte proliferation,migration and apoptosis by inhibiting insulin-like growth factor 1 expression
Jiapeng YE ; Jianwei WANG ; Mao WU ; Shaoshuo LI ; Guopeng WANG ; Haotian WANG ; Zhi TANG ; Yang SHAO
Chinese Journal of Tissue Engineering Research 2024;28(25):4048-4053
BACKGROUND:The alteration of miR-146a-3p level is a common event in the pathogenesis of most neurological diseases,and the specific mechanism of miR-146a-3p regulation of astrocytes has not been studied. OBJECTIVE:To verify that miR-146a-3p regulates astrocyte proliferation,migration and apoptosis through insulin-like growth factor 1. METHODS:12 SD rats were divided into a sham operation group and a spinal cord injury group,with six rats in each group.RNA sequencing analysis was performed on the spinal cord tissues of all groups 2 weeks after surgery to screen out the differential genes(log2FC>2),and to select spinal cord injury-related genes(Score>20)in the Genecards database,and then to predict the target genes of miR-146a-3p by Targetscan.The intersection of three gene sets was obtained to screen out insulin-like growth factor 1 as one of the important target genes.qPCR,western blot assay and immunohistochemistry were performed to analyze the expression level of insulin-like growth factor 1 in spinal cord tissues.The primary astrocytes were divided into NC group,NC-mimics group and miR-146a-3p mimics group.Annexin-V/PI staining was used to detect cell apoptosis.CCK-8 assay was used to detect cell proliferation.Transwell assay was used to detect cell migration ability. RESULTS AND CONCLUSION:The expression of miR-146a-3p in the spinal cord tissue of the spinal cord injury group was lower than that of the sham operation group(P<0.05).The expression of insulin-like growth factor 1 in the spinal cord tissue of the spinal cord injury group was higher than that of the sham operation group(P<0.05).Compared with the NC group and NC-mimics group,the apoptotic rate of astrocytes was increased(P<0.01);the proliferation of astrocytes was decreased(P<0.01)and the number of migration was decreased(P<0.01)in the miR-146a-3p mimics group.To conclude,the expression of miR-146a-3p decreased and the expression of insulin-like growth factor 1 increased in spinal cord tissue after spinal cord injury.miR-146a-3p targeted regulation of insulin-like growth factor 1 in astrocytes,inhibited the proliferation and migration of astrocytes and promoted their apoptosis.
8.Postoperative pulmonary infection in elderly patients with hip fracture:construction of a nomogram model for influencing factors and risk prediction
Haotian WANG ; Mao WU ; Junfeng YANG ; Yang SHAO ; Shaoshuo LI ; Heng YIN ; Hao YU ; Guopeng WANG ; Zhi TANG ; Chengwei ZHOU ; Jianwei WANG
Chinese Journal of Tissue Engineering Research 2024;28(36):5785-5792
BACKGROUND:Establishing a nomogram prediction model for postoperative pulmonary infection in hip fractures and taking early intervention measures is crucial for improving patients'quality of life and reducing medical costs. OBJECTIVE:To construct a nomogram risk prediction model of postoperative pulmonary infection in elderly patients with hip fracture,and provide theoretical basis for feasible prevention and early intervention. METHODS:Case data of 305 elderly patients with hip fractures who underwent surgical treatment at Wuxi Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine between January and October 2020(training set)were retrospectively analyzed.Using univariate and multivariate logistic regression analysis and Hosmer-Lemeshow goodness of fit test,receiver operating characteristic curve was utilized to analyze the diagnostic predictive efficacy of independent risk factors and joint models for postoperative pulmonary infections.Tools glmnet,pROC,and rms in R Studio software were applied to construct a nomogram model for predicting the risk of postoperative pulmonary infection in elderly patients with hip fractures,and calibration curves were further drawn to verify the predictive ability of the nomogram model.Receiver operating characteristic curves,calibration curves,and decision curves were analyzed for 133 elderly patients with hip fractures(validation set)receiving surgery at the same hospital from November 2022 to March 2023 to further predict the predictive ability of the nomogram model. RESULTS AND CONCLUSION:(1)The postoperative pulmonary infection rate in elderly patients with hip fractures in this group was 9.18%(28/305).(2)Single factor and multivariate analysis,as well as forest plots,showed that preoperative hospitalization days,leukocyte count,hypersensitive C-reactive protein,and serum sodium levels were independent risk factors(P<0.05).The Hosmer-Lemeshow goodness of fit test showed good fit(χ2=4.57,P=0.803).Receiver operating characteristic curve analysis was conducted on the independent risk factors and their joint models mentioned above,and the differentiation of each independent risk factor and joint model was good,with statistical significance(P<0.05).(3)The graphical calibration method,C-index,and decision curve were used to validate the nomogram prediction model.The predicted calibration curve was located between the standard curve and the acceptable line,and the predicted risk of the nomogram model was consistent with the actual risk.(4)The validation set used receiver operating characteristic curve,graphic calibration method,and decision curve to validate the prediction model.The results showed good consistency with clinical practice,indicating that the model had a good fit.The nomogram risk prediction model constructed for postoperative pulmonary infection in elderly patients with hip fractures has good predictive performance.The use of the nomogram risk prediction model can screen high-risk populations and provide a theoretical basis for early intervention.
9.Effects of Qiangxin decoction on myocardial mitochondrial homeostasis and energy metabolism in chronic heart failure rats
Yan PANG ; Meiling MAO ; Jianqi LU ; Jiayong CHEN ; Meiling TANG ; Puwei HUANG
China Pharmacy 2024;35(15):1831-1836
OBJECTIVE To investigate the effects of Qiangxin decoction on myocardial mitochondrial and energy metabolism in rats with chronic heart failure (CHF) based on mitophagy. METHODS Male SD rats were collected to establish CHF model by ligating the left anterior descending branch of coronary artery. The successful modeling rats were divided into model group, Qiangxin decoction group [12.25 g/(kg·d), calculated by crude drug], captopril group [10.38 mg/(kg·d)], and Qiangxin decoction+captopril group (the same usage and dosage as single drug group) according to a random number table method, with 8 rats in each group. Another 8 normal rats were selected and received threading in the left anterior descending branch of the coronary artery without ligation as the sham operation group. Starting from the second day after successful modeling, the rats in administration groups were given relevant drug intragastrically, twice a day, for consecutive 28 days. After the last medication, the levels of adenosine triphosphate (ATP), adenosine monophosphate (AMP) and free fatty acid (FFA) in infarcted myocardial tissues were detected, the pathological changes and mitochondrial morphology of the infarcted myocardial tissue were observed, as well as the protein expressions of B cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), TANK-binding kinase 1 (TBK1), p62 were detected in each group. RESULTS Compared with the sham operation group, the infarcted myocardial tissue fibrosis was changed evidently, with a large number of mitochondrial swelling and fusion, and internal cristae rupture; the levels of AMP and FFA, the protein expressions of Bax and p62 were all increased or up-regulated significantly in infarcted myocardial tissue, while the level of ATP, and the protein expressions of Bcl-2 and TBK1 were all decreased or down-regulated significantly (P<0.05). Compared with the model group, the pathological changes of infarcted myocardial tissue and mitochondrial swelling had been improved; the levels of AMP and FFA, and the protein expressions of Bax and p62 in infarcted myocardial tissue were significantly decreased or down-regulated in administration groups, while the level of ATP, and the protein expressions of Bcl-2 and TBK1 were increased or up-regulated significantly (P<0.05). And the effect of Qiangxin decoction+captopril group was better than that of single drug group. CONCLUSIONS Qiangxin decoction can alleviate myocardial fibrosis and mitochondrial swelling in CHF rats, and improve their myocardial energy metabolism, which may be related to regulating the expression of Bcl-2, Bax, TBK1 and p62 proteins and promoting myocardial mitophagy.
10.Survival characteristics of patients with high-risk myelodysplastic syndromes treated with an arsenic-containing herbal combination
Nan JIN ; Yue MAO ; Yan LYU ; Zhuo CHEN ; Dexiu WANG ; Weiyi LIU ; Chi LIU ; Xudong TANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):709-720
Objective To investigate the clinical characteristics of survival in patients with high-risk myelodysplastic syndromes(HR-MDS)and provide a reference for the clinical prognosis of patients with HR-MDS.Methods General data,blood routine test,bone marrow smear with histopathology,cytogenetics,and other clinical data of 200 patients diagnosed with HR-MDS at Xiyuan Hospital of China Academy of Chinese Medical Sciences,during the period of January 2016-September 2022,were retrospectively analyzed.The included patients were categorized into the arsenic-containing herbal combination combined with demethylating agents(HMAs)treatment group and the arsenic-containing Chinese medicine compound combined with androgen treatment group.The influence of clinical indices on the survival characteristics of each group was analyzed.Results Comparison of the impact of clinical indicators on survival in 200 patients with HR-MDS who were treated with arsenic-containing herbal compounds in combination with HMAs or androgens showed that high-risk vs.very high-risk(P=0.018),hemoglobin(Hb)<80 g/L vs.Hb≥80 g/L(P=0.035),platelet(PLT)counts<50×109 L-1 vs.PLT counts≥50×109 L-1(P<0.001),and the difference in median progression-free survival(PFS)time between myelodysplastic syndromes converted to leukemia(MDS-AML)and non-MDS-AML(P=0.003)were statistically significant.Comparison of survival effects of clinical indicators in 68 patients with HR-MDS who were treated with arsenic-containing Chinese medicine compound combined with HMAs showed that the difference in median PFS between PLT count<50×109 L-1 and PLT count≥50×109 L-1(P<0.001)and the difference in median PFS between<5 and≥5 courses of chemotherapy(P=0.018)were statistically significant.Comparison of survival effects of clinical indicators in 132 patients with HR-MDS who were treated with arsenic-containing Chinese medicine compound combined with androgens showed that Hb<80 g/L and Hg≥80 g/L(P=0.028),PLT count<50×109 L-1 and PLT count≥50×109 L-1(P=0.002),and the mean differences in PFS between MDS-AML and non-MDS-AML(P=0.024)were statistically significant.Conclusion The clinical characteristics of long-surviving patients treated with arsenic-containing herbal combination in combination with HMAs included PLT counts≥50×109 L-1 and≥5 courses of chemotherapy.The clinical characteristics of long-surviving patients treated with arsenic-containing herbal combination in combination with androgens included Hg≥80 g/L,PLT count≥50×109 L-1,and non-MDS-AML.

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