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.Chinesization of the HEMO-FISS-QoL questionnaire and its reliability and validity
Songpeng SUN ; Shan JIA ; Fangfang XU ; Tianyu LI ; Zhiyun ZHANG ; Qiaorong CAO ; Xinjian LI ; Yao WU ; Weiping WAN ; Bin SHI ; Jianguo WANG ; Hong NI ; Longyu LIANG ; Xingxiao HUO ; Tianqing YANG ; Lei TIAN ; Ying TIAN ; Mei LIN ; Zhanjun WANG ; Yangyang ZHOU ; Hongchuan CHU ; Riyu LIAO ; Kuerban XIEYIDA ; Junhong LONG ; Shuxin ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(1):75-82
Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.
3.Association between TyG-WC and risk of coronary heart disease in middle-aged and elderly population:a prospective cohort study with 10-year follow-up
Yu WANG ; Ying MIAO ; Qiang LIN ; Mao TIAN ; Zhuang CHEN ; Qin WAN
The Journal of Practical Medicine 2024;40(12):1731-1736
Objective To investigate the association between triglyceride glucose index(TyG)combined with waist circumference(WC)and the risk of new-onset coronary heart disease(CHD)in the middle-aged and elderly people in 10 years of non-interventional follow-up in Luzhou area.Methods A total of 8 647 eligible individu-als participated in epidemiological survey in Luzhou area were selected.The subjects were divided into different groups according to the quartiles of the TyG-WC and followed for ten years.The correlation between different TyG-WC quartile group and 10-year new CHD in middle-aged and elderly population was analyzed by using univariate analy-sis and Cox regression analysis.Results Of the 8 647 participants in the study,484 had new CHD,accounting for 5.5%.The comparison of the number of newly diagnosed CHD subjects grouped by TyG-WC quartiles indicated the 4th quartile group>the 3rd quartile group>the 2nd quartile group>the 1st quartile group,showing statistical significance(P<0.001).Cox regression analysis showed that without adjusting for any variables,the risk of new CHD in 10 years increased with the increase of TyG-WC quartile group,and the differences between the second,third and fourth quartile array and the first quartile array were statistically significant(P<0.05).After adjusting for age and sex and further adjusting for the influence of various influencing factors,the risk of new CHD in 10 years increased with the increase of TyG-WC quartile group.The difference between the third and fourth quartile array and the first quartile array was statistically significant(P<0.05).Conclusion TyG-WC is a risk factor for new-onset CHD in the middle-aged and elderly population in Luzhou area in 10 years of non-interventional follow-up,and TyG-WC may be a predictor of the risk of CHD in the middle-aged and elderly population.
4.Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors
Xiao LIU ; Ying CAO ; Wan Xiao LIN ; Yang Dan GAO ; Hui Hui MIAO ; Zuo Tian LI
Biomedical and Environmental Sciences 2024;37(2):133-145
Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples. Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively."Pyruvate""alpha-linolenic acid"and"2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine"are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.
5.Standardized operational protocol for the China Human Brain Bank Consortium(2nd edition)
Xue WANG ; Zhen CHEN ; Juan-Li WU ; Nai-Li WANG ; Di ZHANG ; Juan DU ; Liang YU ; Wan-Ru DUAN ; Peng-Hao LIU ; Han-Lin ZHANG ; Can HUANG ; Yue-Shan PIAO ; Ke-Qing ZHU ; Ai-Min BAO ; Jing ZHANG ; Yi SHEN ; Chao MA ; Wen-Ying QIU ; Xiao-Jing QIAN
Acta Anatomica Sinica 2024;55(6):734-745
Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.
6.Serological Characteristics and Clinical Significance of Irregular Antibodies in Pregnant Women
Tao ZHANG ; Gui-Lin YANG ; Hong-Peng ZHANG ; Ying-Ying WU ; Sheng-Lan LI ; Kuai WAN ; Hai-Feng QI ; Chun-Li LI
Journal of Experimental Hematology 2024;32(1):231-236
Objective:To understand the serological characteristics of irregular antibodies in pregnant women and explore their clinical significance.Methods:From January 2017 to March 2022,151 471 pregnant women in Women and Children's Hospital of Chongqing Medical University were enrolled in this study,microcolumn gel card test was used for irregular antibody screening,and antibody specificity identification was further performed in some antibody-positive subjects.Results:The positive rate of irregular antibody screening in the enrolled pregnant women was 0.91%(1 375/151 471),0.23%(355/151 471)was detected in the first trimester,0.05%(71/151 471)in the second trimester,and 0.63%(949/151 471)in the third trimester.The positive rate of irregular antibody screening in the third trimester was significantly higher than that in the first and second trimester,and a significant increase in the number of positive cases was found in the third trimester than that in the second trimester.The analysis of agglutination intensity of 1 375 irregular antibody screening positive results showed that the weakly positive agglutination intensity accounted for 50.11%(689/1 375),which was the highest,the suspicious positive was 18.69%(257/1 375),and the positive was 31.20%(429/1 375).The significant difference in distribution of agglutination intensity was not observed between the first trimester group and the second trimester group,however,in the third trimester,the proportion of suspicious positive and weakly positive was lower than the first trimester,while,the proportion of positive was higher than the first trimester,and the difference was statistically significant(P<0.001).Among the irregular antibody screening positive pregnant women,the proportion of pregnant women with pregnancy number ≥ 2 was significantly higher than that with pregnancy≤1.Among 60 pregnant women who underwent antibody identification,the distributions of the antibodies were as follows:Rh blood group system accounted for 23.33%(14/60),Lewis system 43.33%(26/60),Kidd system 3.33%(2/60),MNS system 16.67%(10/60),P1PK system 1.67%(1/60),autoantibodies 1.67%(1/60),and 4 cases was unable to identify(6.67%,4/60).Among specific antibodies,the anti-Lea was the most common(30.00%),followed by anti-E(16.67%)and anti-M(16.67%).Conclusion:The differences of irregular antibody serological characteristics exist in pregnant women from different regions with different genetic backgrounds,understanding the characteristics of irregular antibody in local pregnant women is of great significance for ensuring transfusion safety in pregnant women and preventing hemolytic disease of newborn.
7.Distribution Characteristics of Rh Phenotype and Feasibility of Compatible Blood Transfusion in Pregnant and Postpartum Women
Gui-Lin YANG ; Tao ZHANG ; Chun-Li LI ; Hong-Peng ZHANG ; Ying-Ying WU ; Sheng-Lan LI ; Kuai WAN ; Yun-Ping YANG
Journal of Experimental Hematology 2024;32(3):868-874
Objective:To analyze the distribution characteristics of Rh phenotype in pregnant and postpartum women in Chongqing area,and to explore the clinical significance of Rh phenotype in pregnant and postpartum women and the feasibility of Rh phenotype compatible blood transfusion.Methods:The ABO blood group and Rh phenotype of 65 161 pregnant and postpartum women were detected by microcolumn gel method,and 48 122 males in the same period were taken as controls.The data were analyzed by Chi-square test.Results:There were 112 870 cases(99.64%)of RhD+in 113 283 samples.In RhD+cases,CCDee(48.39%)and CcDEe(32.88%)were the main phenotypes.The first case of D--phenotype in Chongqing area was detected.413 cases(0.36%)of RhD-were detected,with ccdee(52.78%)and Ccdee(33.41%)as the main phenotypes.Compared with RhD-group,RhD+group showed statistically significant difference in Rh phenotype distribution(P<0.01).Among 65 161 maternal samples,the positive rate of 5 antigens of Rh blood group from high to low was D>e>C>c>E,and there was no significant difference compared with male samples(P>0.05).There was no significant difference in the distribution of Rh phenotype between males and pregnant/postpartum women,as well as between pregnant/postpartum women with different ABO blood groups(P>0.05).In pregnant and postpartum women,there was no significant difference in distribution of Rh phenotype among the normal pregnancy population,the population with adverse pregnancy history,the population using human assisted reproductive technology(ART)and the population with infertility(P>0.05).There was no significant difference in the distribution of Rh phenotype between the 4 populations mentioned above and the inpatients in the local general Grade A hospitals and the blood donors(P>0.05).In RhD positive pregnant and postpartum women,the probability of finding compatible blood for CcDEe phenotype was 100%,the probability of finding compatible blood for CCDee,CcDee and CCDEe phenotypes was 45%-60%,the probability of finding compatible blood for ccDEE,ccDEe and CcDEE phenotypes was 5%-10%,and the probability of finding compatible blood for other phenotypes was lower than 0.5%.The supply of blood with CCDee and ccDEE phenotypes can meet the compatible transfusions requirements of 7 Rh phenotypes in more than 99%of patients.Conclusion:Rh phenotype detection should be carried out for pregnant and postpartum women,and it is feasible to carry out Rh phenotype-matched or compatible blood transfusion for pregnant and postpartum women who need blood transfusion.
8.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
9.Research status of Erchen Decoction in the treatment of respiratory diseases
Wan-Lin YANG ; Ying-Shan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(8):1236-1240
Erchen Decoction is derived from"Taiping Huimin and Prescription Bureau",which is mainly composed of pinellia,Tangerine peel,poria and licorice and other traditional Chinese medicine.Its main effect is to dry dampness and reduce phlegm,regulate qi and middle,and is the basic prescription for the treatment of dampness and phlegm syndrome.A large number of studies have confirmed that Erchen Decoction has a good effect on multiple respiratory diseases.At present,Erchen Decoction has a good clinical effect on respiratory diseases such as COPD,asthma,bronchitis,cough and lung cancer,and its mechanism of action may be related to anti-inflammatory,anti-tumor,anticough,improvement of airway mucus secretion and anti-oxidation.In this paper,the clinical and animal experimental studies on the treatment of respiratory diseases by Erchen Decoction in recent years are summarized.
10.Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program
Ming-Ying LU ; Chung-Feng HUANG ; Chao-Hung HUNG ; Chi‐Ming TAI ; Lein-Ray MO ; Hsing-Tao KUO ; Kuo-Chih TSENG ; Ching-Chu LO ; Ming-Jong BAIR ; Szu-Jen WANG ; Jee-Fu HUANG ; Ming-Lun YEH ; Chun-Ting CHEN ; Ming-Chang TSAI ; Chien-Wei HUANG ; Pei-Lun LEE ; Tzeng-Hue YANG ; Yi-Hsiang HUANG ; Lee-Won CHONG ; Chien-Lin CHEN ; Chi-Chieh YANG ; Sheng‐Shun YANG ; Pin-Nan CHENG ; Tsai-Yuan HSIEH ; Jui-Ting HU ; Wen-Chih WU ; Chien-Yu CHENG ; Guei-Ying CHEN ; Guo-Xiong ZHOU ; Wei-Lun TSAI ; Chien-Neng KAO ; Chih-Lang LIN ; Chia-Chi WANG ; Ta-Ya LIN ; Chih‐Lin LIN ; Wei-Wen SU ; Tzong-Hsi LEE ; Te-Sheng CHANG ; Chun-Jen LIU ; Chia-Yen DAI ; Jia-Horng KAO ; Han-Chieh LIN ; Wan-Long CHUANG ; Cheng-Yuan PENG ; Chun-Wei- TSAI ; Chi-Yi CHEN ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(1):64-79
Background/Aims:
Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy.
Methods:
We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment.
Results:
The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset.
Conclusions
Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

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