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.Effects of Moxibustion at "Guanyuan (CV 4)" on Oxidative Stress and Autophagy-Related Gene Expression of Skin Tissue in Photoaging Model Rats
Qianqian HUI ; Yuan JING ; Sijie OUYANG ; Shijing YOU ; Boying TONG
Journal of Traditional Chinese Medicine 2025;66(6):621-628
ObjectiveTo explore the potential mechanism of moxibustion at Guanyuan (CV 4) in delaying skin photoaging. MethodsThirty-two male Wistar rats were randomly divided into four groups, namely blank group, model group, vitamin E group, and moxibustion group, with 8 rats in each group. Except for the blank group, dorsal skin of rats were exposed to ultraviolet (UV) radiation to establish a skin photoaging model. One week after modeling, the moxibustion group received moxibustion at "Guanyuan (CV 4)" once a day, five days per week; the vitamin E group received vitamin E (25 mg/kg·d) once a day by gavage, five days per week; the blank group, model group, and moxibustion group received an equivalent volume of normal saline via gavage; the intervention lasted for 7 weeks. After 7 weeks, dorsal skin tissues were collected to analyze the following indicators, such as skin tissue moisture content, histomorphological changes using hematoxylin-eosin (HE) staining, Collagen Ⅰ and collagen Ⅲ content using ELISA. Malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), hydrogen peroxide (H2O2), and catalase (CAT) activity in skin tissue were dectected. Western Blot was used to determin autophagy-related proteins, including microtubule-associated protein 1A/1B-light chain 3 (LC3), polyubiquitin-binding protein (p62), and autophagy-specific gene (Beclin-1); LC3, p62, and Beclin-1 mRNA expression was detected via qRT-PCR, and autophagosome formation was observed using transmission electron microscopy (TEM). ResultsHE staining showed that the epidermal structure in the blank group was orderly and evenly thick, while the model group exhibited uneven epidermal thickness. In the moxibustion group, the epidermis was well-structured, smooth, and uniform, with densely arranged dermal layers; the epidermis in the vitamin E group was thicker than that in the model group. Compared with the blank group, the model group exhibited decreased skin moisture content and reduced level of Collagen Ⅰ and collagen Ⅲ, reduced SOD, CAT, and GSH-Px activity in skin tissue, increased H2O2 and MDA activity, elevated p62 protein and mRNA expression, reduced LC3 and Beclin-1 protein and mRNA expression (P<0.05 or P<0.01). Compared with the model group, the moxibustion group showed significant improvement in all these indicators (P<0.05 or P<0.01); whereas the vitamin E group did not show a statistically significant difference in Collagen Ⅰ and collagen Ⅲ levels (P>0.05). TEM results showed that, compared with the blank group, the model group had atrophic skin cells, extensive mitochondrial vacuolization, and degraded cellular structures; the moxibustion group exhibited crescent- or cup-shaped autophagosomes with a significantly increased number of autophagosomes per unit area, whereas the vitamin E group showed less improvement than the moxibustion group. ConclusionMoxibustion at "Guanyuan (CV 4)" may alleviate skin photoaging by regulating oxidative stress imba-lance, modulating cellular autophagy, and promoting collagen synthesis, thereby slowing the aging process of the skin.
3.Celastrol directly targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression.
Yuyu ZHU ; Lixin ZHAO ; Wei YAN ; Hongyue MA ; Wanjun ZHAO ; Jiao QU ; Wei ZHENG ; Chenyang ZHANG ; Haojie DU ; Meng YU ; Ning WAN ; Hui YE ; Yicheng XIE ; Bowen KE ; Qiang XU ; Haiyan SUN ; Yang SUN ; Zijun OUYANG
Acta Pharmaceutica Sinica B 2025;15(2):876-891
Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.
4.Parabacteroides distasonis promotes liver regeneration by increasing β-hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals.
Manlan GUO ; Xiaowen JIANG ; Hui OUYANG ; Xianglong ZHANG ; Shuaishuai ZHANG ; Peng WANG ; Guofang BI ; Ting WU ; Wenhong ZHOU ; Fengting LIANG ; Xiao YANG ; Shicheng FAN ; Jian-Hong FANG ; Peng CHEN ; Huichang BI
Acta Pharmaceutica Sinica B 2025;15(3):1430-1446
The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.
5.Role of Folic Acid Supplementation on Association between Short Inter-Pregnancy Intervals and Adverse Birth Outcomes: A Retrospective Cohort Study in Changsha, China.
Zhi Qing ZHAO ; Ling CHEN ; Wen Bin OUYANG ; Jing DENG ; Xiao Hui CHEN ; Xin HUANG
Biomedical and Environmental Sciences 2025;38(6):751-756
6.Research hotspots and prospects of integrating traditional Chinese medicine culture into ideological and political education from 2013 to 2022
Shan HUI ; Yonggang WU ; Yifan HU ; Jing OUYANG
Chinese Medical Ethics 2024;37(3):359-365
By analyzing information such as the number of publications,authors,institutions and keywords in the literature on the integration of traditional Chinese medicine(TCM)culture into ideological and political education in the past 10 years,it was found that the overall number of publications showed an increasing trend. As the main research fronts,TCM colleges and universities had not yet formed teams in cooperation with other universities. The research hotspots were relatively concentrated,but the research horizons were not broad enough. It is suggested that in the future,policy should be taken as the guide to build a cross-regional interdisciplinary cooperation system,horizontally and vertically extend research subjects,innovate and construct diversified teaching models,continue to deeply explore and organically integrate ideological and political education elements,continuously improve the evaluation system of educational functions,and further enhance the timeliness of integrating traditional Chinese medicine culture into ideological and political education. So as to make greater contributions to cultivating talents in the new era and promoting the inheritance and innovation of TCM culture.
7.Prediction model of uroschesis rate after radical cervical cancer resection based on machine learning
Hui ZHANG ; Yanqiong OUYANG ; Xiuhua HUANG
Chinese Journal of Practical Nursing 2024;40(7):520-526
Objective:To construct a risk prediction model for urinary retention in patients undergoing radical cervical cancer surgery based on machine learning, and the prediction effect of the model was internally verified and evaluated, in order to provide reference for the early prevention and treatment of urinary retention in patients undergoing radical cervical cancer surgery.Methods:A total of 981 patients who underwent radical cervical cancer surgery in the First Affiliated Hospital of Anhui Medical University from June 2017 to February 2022 were selected and divided into the training set (687 cases) and the test set (294 cases) according to a ratio of 7∶3. Through literature review and risk factor analysis, the influencing factors of urinary retention after radical treatment of cervical cancer were explored, and the risk prediction model of urinary retention was constructed by using XGBoost, random forest, support vector machine and decision tree in machine learning. The accuracy rate, recall rate, F1 value and AUC of four machine learning algorithms were calculated by using the method of 10-fold cross-validation, and the model with the highest predictive efficiency was selected.Results:Among the 981 patients included, the incidence of urinary retention after radical cervical cancer surgery was 18.86% (185/981). The median age of urinary retention group was 51 years old, and that of non urinary retention group was 50 years old. Statistically significant variables in the univariate analysis and influencing factors summarized by literature review were featured, including patient age, intraoperative blood loss, body mass index (BMI), cancer stage, surgical method, surgical resection scope, whether pelvic lymph node dissection was performed, comorbidities and residual urine. Among the four model building methods of machine learning, the random forest model has the best effect, its training set F1 value was 0.94, the test set F1 value was 0.77, the ROC was plotted and the AUC was calculated to be 0.73. Age, intraoperative blood loss, BMI, cancer stage and surgical method contributed significantly to the classification of random forest model.Conclusions:The prediction model of urinary retention risk after radical cervical cancer surgery based on random forest method has the best efficacy. It is useful to help nursing personnel evaluate the risk of the uroschesis for a patient and then take targeted nursing interventions to actively prevent postoperative urinary retention.
8.Study on gentamicin sulfate regulating gut microbiota for affecting glucose and lipid metabolism and inflammation to improve hypertension in rats
Hui OUYANG ; Guixiu CHEN ; Shirui XIONG ; Xingchun ZHU
Chongqing Medicine 2024;53(8):1126-1131
Objective To investigate the relationship between gentamicin sulfate mediated gut microbi-ota in affecting glucolipid metabolism and inflammation with hypertension improvement.Methods Sprague-Dawley rats (8-weeks-old) were divided into the normal diet group (ND,n=11),high fat diet group (HFD,n=13) and HFD combined with gentamicin sulfate gavage group (GS,n=13).Blood pressure was monitored weekly during 5-13 weeks,and the levels of insulin,IL-1β,IL-6,TNF-α,LPS,TC,TG,LDL-C,HDL-C and homeostasis model assessment of insulin resistance index (HOMA-IR) were assessed at 13 weeks.The met-agenomic analyses were performed on DNA samples from rat colonic feces.Results The blood pressure in 13 weeks had no statistical difference among the three groups (P>0.05).The blood pressure during 5-10 weeks in the GS group was higher than that in the ND group with statistical difference (P<0.05).The blood pressure during 5-13 weeks in the HFD group was higher than that in the ND group,and the blood pressure during 10-13 weeks in the GS group was lower than that in the HFD with statistical difference (P<0.05). Compared with the group ND,the levels of TC,TG,LDL-C and HOMA-IR in the HFD group were higher,the HDL-C level was lower,and the differences were statistically significant (P<0.05).Compared with the HFD group,the levels of TG,LDL-C and HOMA-IR in the GS group were lower,the HDL-C level was higher,and the differences were statistically significant (P<0.05).The levels of LPS,IL-1β,IL-6 and TNF-α in the HFD group were higher than those in the ND group,while the GS group was lower than the HFD group (P<0.05).The partial least squares discriminant analysis showed that the intestinal microbiota in the HFD group and GS group was different in structure from that in the ND group.The family level results showed that the structure of the gut microbiota changed in three groups,including 24 microbiotas with significant changes.The hierarchical analysis showed that the proportion of f-desulphovibrio in the HFD group was higher than that in the ND group,while the GS group was lower the HFD group,and the differences were statistically significant (P<0.05).Conclusion Oral antibiotic gentamicin sulfate could improve the glucose and lipid metabolism ab-normalities and inflammation caused by HFD and its mechanism may be to relieve hypertension by regulating intestinal flora structure,abundance and LPS level.
9.Relationship between post-traumatic stress disorder and sleep
Jingye ZHAN ; Runda JIAO ; Hui OUYANG ; Weizhi LIU ; Lili WU
Academic Journal of Naval Medical University 2024;45(9):1147-1155
Post-traumatic stress disorder (PTSD),with the principal manifestations as invasive thinking,avoidance,negative emotions and cognition,and increased alertness,is a psychological disorder occurring after traumatic events. Sleep disorders are also considered as one of the core characteristics of PTSD. Previous studies have partly revealed the relationship between PTSD and sleep disorders,but the physiological mechanism of the relationship is still unclear. This article provides an overview of the clinical and physiological characteristics of PTSD and sleep disorders. Based on this,the bidirectional relationship between PTSD and sleep disorders is discussed,and the relevant physiological and brain mechanisms of the relationship between them are further explored. Future research needs to explore the neurophysiological mechanisms underlying the bidirectional relationship between PTSD and sleep by exploring the brain regions and neural circuits associated with both PTSD and sleep,providing more information and methods for the prevention and treatment of PTSD and sleep disorders.
10.Prevalence and risk factors of post-traumatic stress disorder 1 year after trauma exposure
Lili WU ; Ao FEI ; Yan WANG ; Weizhi LIU ; Hui OUYANG
Academic Journal of Naval Medical University 2024;45(10):1266-1271
Objective To observe the change in the prevalence of post-traumatic stress disorder(PTSD)1 year after trauma exposure and analyze the risk factors of PTSD 1 year after trauma exposure.Methods Convenience sampling was conducted at the initial outbreak of the coronavirus disease 2019 epidemic and 1 year later,respectively.Participants participated in the anonymous online survey.The survey consisted of 2 self-completed questionnaires:1 collected personal information(gender,age,education level,occupation)and subjective sleep quality;the other is the PTSD checklist(PCL-5)from the Diagnostic and Statistical Manual of Mental Disorders,5th edition.Valid questionnaires of 2 091 and 2 092 were respectively retrieved at the initial stage of trauma exposure and 1 year later.Results The prevalence of PTSD at the initial stage of trauma exposure was 5.3%(111/2 091)and 1 year after trauma exposure was 19.1%(399/2 092).Multiple linear regression analysis showed that age(P<0.01),gender(P<0.01),and subjective sleep quality(P<0.01)were risk factors related to PTSD.Conclusions One year after trauma exposure,the prevalence of PTSD increases.Psychological intervention measures should be given at the early stage of trauma exposure,and special attention should be paid to young individuals,women,and those with sleep disorders.

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