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.Establishing a risk prediction model for the onset of female stress urinary incontinence based on machine learning
Xinran SHI ; Zhen PANG ; Ting QIAO ; Jingjing LI ; Qinzhang WANG
Journal of Modern Urology 2025;30(3):196-206
Objective: To construct prediction models of female stress urinary incontinence (SUI), and evaluate the efficacy of each model, so as to provide reference for the early diagnosis of SUI. Methods: Female SUI patients treated in our hospital during Oct. 2019 and Oct. 2023 and healthy women undergoing physical examination during the same period were involved. Women 42 days after delivery were included in the postpartum group (n=611), and perimenopausal and postmenopausal women were included in the non-postpartum group (n=409). The number of random seeds was set and the participants were divided into the training and verification sets in a ratio of 7∶3. Relevant clinical data were collected, and meaningful variables were screened using single factor and Lasso regression, which were then incorporated into the K-nearest neighbor method (KNN), support vector machine (SVM),decision tree (DT) and random forest (RF) algorithms. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) of the models were calculated to screen out the optimal model. Results: There were 352 SUI patients (57.6%) in the postpartum group. According to single factor and Lasso regression, significant variables included age, body mass index (BMI), maximum rapid muscle stage, parity, bladder neck mobility (BND), urethral rotation angle (URA), lateral perineal incision, past incontinence, and constipation. In the verification set, the AUC of KNN,SVM,DT and RF models were 0.881,0.878,0.750 and 0.905,respectively; the AUC, accuracy, F1 index and Kappa value of RF model were the largest. In the non-postpartum group, there were 260 SUI patients, accounting for 63.6%. The significant variables were age,BMI, maximum value and recovery time of fast muscle stage, mean value of slow muscle stage, post-resting stage variability, vaginal delivery, past incontinence, and constipation. In the verification set, the AUC of KNN,SVM,DT and RF models were 0.819,0.805,0.603 and 0.830, respectively; the AUC, accuracy, Kappa value of the RF model were the largest. Conclusion: This study successfully established 4 prediction models for the incidence of SUI in women at 42 days postpartum, perimenopausal and postmenopausal women based on machine learning. Among them, the model adopting the RF algorithm had the best prediction efficiency.
3.Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma: A Review
Han YANG ; Yonghuang YAN ; Wenting ZHANG ; Peixuan ZHU ; Fang YAN ; Yujie WU ; Shiqing QIAO ; Tieshan WANG ; Zeqi SU ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):206-212
Cough variant asthma (CVA) is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation, and its pathogenesis involves environmental, genetic, immune, and other factors. In recent years, the advantages of traditional Chinese medicine (TCM) in the treatment of CVA have attracted the attention of experts and scholars in China and abroad, especially its prominent role in regulating immune balance, relieving cough symptoms in CVA patients, and reducing recurrence. T Helper cells 1 (Th1), T helper cells 2 (Th2), T helper cells 17 (Th17), and regulatory T cells (Treg) are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions, maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells (Th0) can be differentiated into Th1, Th2, Th17, Treg, and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function, and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper, the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile, the latest research on the regulation of immune imbalance by TCM compound, single TCM, and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA, as well as the development of clinical treatment and basic research of CVA.
4.Protective effects of Silybum thistle extract and related formulations on liver in mice with alcoholism
Ting-Qiao WANG ; Wu-Jiang REN ; Liang-Yu LÜ ; Rong WEI ; Yue-Yi GUO ; Jian ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(7):1009-1013
Objective To investigate the protective effect of silymarin extract(SME)and its complex preparation on ethanol liver injury.Methods An ethanol liver injury model was established by gavage of 12 mL·kg-1 50%ethanol.Male mice were divided into blank group(distilled water),model group(ethanol liver injury model),SME-L,-H groups(6,20 mg·mL-1 SME),SME+Ganoderma lucidum extract(GLE)-L,-H groups(10,30 mg·mL-1 SME+GLE,SME∶GLE=1∶1),Jian An Shi Silymarin Pueraria Mirifica and Tansy tablets(JAS)-L,-H groups(68,204 mg·mL-1 JAS),there were 12 mice in each group.The serum levels of glutamic-oxaloacetic transaminase(GOT)in mice were measured by fully automated biochemical analyzer assay;the serum levels of interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in mice were measured by enzyme-linked immunosorbent assay(ELASA);the hepatic tissue of oxidative stress indexes[catalase(CAT)and total superoxide dismutase(T-SOD)]were measured by ultraviolet spectrophotometer.Results The T-SOD activity in the blank group,model group,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were(192.54±49.00),(141.65±34.72),(205.83±32.77),(191.68±25.83),(192.31±28.79),(177.82±32.61),(218.58±74.80)and(210.24±31.65)U·mg·prot-1;CAT activity were(37.78±5.73),(28.92±8.44),(44.12±11.52),(41.41±9.15),(47.01±10.48),(41.63±8.95),(47.14±8.91)and(48.29±10.06)U·mg-1;GPT levels were(47.61±13.00),(97.84±26.00),(62.33±18.92),(51.84±17.91),(70.77±28.00),(58.00±21.27),(52.28±18.78)and(45.55±9.27)U·L-1;IL-6 levels were(21.03±1.52),(28.43±5.75),(21.90±3.24),(21.23±1.55),(22.26±2.58),(21.24±2.91),(22.17±4.14)and(21.14±3.02)pg·mL-1.Comparing the above indexes in the model group with the blank group,and comparing the above indexes in the SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L,JAS-H groups with the model group,the differences were statistically significant(all P<0.01).The TNF-α levels in blank,model,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were were(28.07±7.72),(69.02±16.34),(40.29±8.94),(48.84±10.17),(41.91±14.96),(40.07±12.75),(50.72±11.44)and(45.05±11.34)pg·mL-1.Comparing the model group with the blank group,the SME,SME+GLE-L,-M and JAS,-M groups with the model group,the differences were statistically significant(all P<0.01).Conclusion Silybum marianum extract and its compound preparation can increase the antioxidant level and reduce the inflammation of mouse liver,and have a certain improvement effect on liver injury caused by acute ethanol poisoning.
5.Establishment and management of health room in primary and secondary schools in Jilin Province
WANG Qiao, YANG Shujuan, ZHANG Yiquan, ZHANG Peibin, YU Miao, LIU Yunjuan, CUI Ting
Chinese Journal of School Health 2024;45(12):1681-1685
Objective:
To understand the current situation of health rooms in primary and secondary schools in Jilin Province, so as to provide the data support for scientific decision making.
Methods:
From April to July 2023, 512 primary and secondary schools and 1 432 school doctors and health care teachers were selected through convenience sampling method in Jilin Province to conduct an electronic questionnaire survey, including the basic information of the school, the situation of health rooms, personnel setting, and the development of school health work.
Results:
Among the 512 schools, only 6.4% of the 299 schools that should have clinics had medical institution practice licenses. The compliance rate of clinic area was 16.6%, and the compliance rate of health room area was 75.0%. About 92.1% of the middle schools and 90.6% of the primary schools identified the reporters of infectious diseases, and 90.9% of the primary schools and 85.5% of the secondary schools filed files for students. Totally 73.5% of the staff in the health room were teachers, and only 17.9% were health professionals. Nearly 70.1% of school doctors or health care teachers were engaged in part time jobs, and 60.9% engaged in school health for ≤5 years. In terms of the content in urgent need of training and improvement, the top five were knowledge about first aid (79.7%),infectious disease prevention and treatment( 73.3 %), health education (64.0%), common disease diagnosis (60.1%) and psychological counseling (53.6%).
Conclusions
Health care institutions, equipment and facilities in primary and secondary schools in Jilin Province are inadequate, and the construction of school doctors and health care teachers is in need of improvement. It should pay more attention to school health and work together to optimize the team of school doctors and health care teachers.
6.Feasibility of non-invasive prenatal testing for the detection of fetal chromosomal copy number variants
Ying XUE ; Longwei QIAO ; Quanze HE ; Chunhua ZHANG ; Xiaojuan WU ; Guodong ZHAO ; Ting WANG
Chinese Journal of Medical Genetics 2024;41(6):696-701
Objective:To explore the feasibility of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal copy number variants (CNV).Methods:A retrospective analysis was carried out on NIPT positive samples in Suzhou Municipal Hospital from January 1, 2019 to December 31, 2021. The effect of NIPT on fetal CNV detection was assessed by comparison with the results of karyotype analysis and/or chromosomal microarray analysis (CMA).Results:Among the 525 NIPT positive samples, 146 were CNV cases, of which 84 were further verified by karyotyping and/or CMA, 29(34.5%) were true positive. Among them, 12 cases were pathogenic variants, 2 cases were likely pathogenic variants and 15 cases were variants of uncertain significance.Conclusion:NIPT could detect CNV with high accuracy, and to combine CNV detection and chromosomal aneuploidy detection has great significance to improve the prenatal and postnatal care.
7.A comparative study of different early time of getting out of bed after transradial percutaneous coronary interventions
Li ZHANG ; Rui WANG ; Lijuan QIAO ; Xiaodong XU ; Ting DI ; Yahui GONG
Chinese Journal of Practical Nursing 2024;40(18):1361-1367
Objective:To compare the clinical efficacy of 1 h and 12 h getting out of bed after transradial percutaneous coronary intervention (PCI), and to provide evidence for early safe getting out of bed after PCI.Methods:The quasi-experimental method was used in this study. A total of 84 patients undergoing radial artery PCI in the Cardiovascular Center of the Affiliated Hospital of Gansu University of Chinese Medicine from July 2022 to May 2023 were selected by purpose sampling method, and were divided into the control group and the experimental group by random number table method, with 42 patients in each group. The control group was given 12 h post-operative getting out of bed activity program, and the experimental group was given 1 h post-operative getting out of bed activity program. The quality of life and self-care ability of daily life were compared before and after intervention. Besides patients′ rehabilitation satisfaction was compared after intervention.Results:Ultimately there were 42 patients in each group completed the research. In the control group, there were 24 males, 18 females, aged (66.08 ± 6.78) years old; in the experimental group there were 22 males, 20 females, aged (68.03 ± 7.17) years old. Before intervention, there were no significant differences in quality of life, self-care ability of daily life and adverse cardiac events between 2 groups (all P>0.05). After intervention, the scores of quality of life in physical function, social relationship, emotional function and environment were (77.20 ± 4.17), (42.40 ± 3.71), (68.10 ± 4.74) and (76.90 ± 4.38), respectively. Higher than (74.50 ± 3.91), (40.20 ± 3.94), (67.70 ± 3.88), (74.35 ± 3.41) in the control group, the differences between the two groups were statistically significant ( t values were 2.17-2.98, all P<0.05). The scores of daily self-care ability in grooming, eating, dressing, going to the toilet, going up and down stairs, bed chair transfer and flat walking were (4.62 ± 1.33), (6.37 ± 2.26), (8.00 ± 2.48), (6.25 ± 2.46), (4.62 ± 2.08), (10.12 ± 3.09), (10.50 ± 3.54) points, higher than the control group (4.06 ± 1.96), (5.75 ± 1.79), (6.37 ± 2.26), (5.25 ± 1.10), (3.37 ± 2.62), (8.75 ± 2.19), (8.87 ± 2.11) points. The differences between the two groups were statistically significant ( t values were 2.29-3.30, all P<0.05). The scores of rehabilitation satisfaction of experimental group in rehabilitation treatment effect, team professional level and rehabilitation treatment arrangement were (4.55 ± 0.50), (4.82 ± 0.38), (4.77 ± 0.42) points, respectively, which were higher than (4.20 ± 0.64), (4.47 ± 0.64), (4.40 ± 0.81) points of control group. The differences between the two groups were statistically significant ( t=2.69, 2.96, 2.59, all P<0.05). Conclusions:Getting out of bed 1 h after radial artery PCI is safe and effective, which can significantly improve patients′ quality of life, self-care ability and satisfaction.It is expected to be clinically promoted and trialed.
8.Establishment and evaluation of non-obese polycystic ovary syndrome rat model
Shiqing QIAO ; Ting WANG ; Yonghuang YAN ; Jiusi YANG ; Yuling YU ; Yanmin WANG ; Yateng SUN ; Yujie WU ; Peixuan ZHU ; Min LI ; Cong CHEN ; Zeqi SU ; Cai ZHANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):965-975
Objective To establish a stable rat model of non-obese polycystic ovary syndrome(PCOS)with clinical characteristics.Methods Dehydroepiandrosterone(DHEA)was used to establish a PCOS rat model by subcutaneous injection.Three-week-old female SD rats were divided into a normal group,6 mg/kg DHEA model group,and 60 mg/kg DHEA model group.The model groups were subcutaneously injected with the corresponding dose of DHEA daily,while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days.The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA to induce a PCOS rat model.On this basis,the optimal DHEA modeling dose was selected,and stop and continue modeling groups were set up to observe the model for 28 days and evaluate its maintenance.The stop modeling group was no longer given DHEA,and the continued modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h.The evaluation indicators included body mass,estrous cycle,fasting blood glucose,serum insulin,histopathologic morphology of the ovaries,and serum sex hormone levels.Results(1)Compared with the normal group,the 6 mg/kg and 60 mg/kg DHEA model groups showed no significant difference in body mass,and their estrous cycles were irregular.There were more cystically dilated large follicles in the ovaries;fewer mature follicles;reduced layers of granulosa cells,which were arranged in a sparse and disorganized manner;and fewer lutea in the 6 mg/kg and 60 mg/kg DHEA model groups than the normal group.Furthermore,serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group(P<0.05)than the normal group.(2)The stop modeling group(A2 group)resumed regular estrous cycles after 2 weeks,various growth follicles and corpora lutea were observed in the ovarian tissues,the number of cystic follicles was reduced,the number of granulosa cell layers increased,mature follicles were visible,oocyte morphology was locally intact,and the levels of E2 and AMH were reduced compared with the normal group(A1 group)(P<0.05).(3)The continue model group(B2 group)was in the late stage of estrous cycle for a long period,and there were more large follicles with cystic dilatation,fewer mature follicles,fewer layers of granulosa cells with a sparse and disordered arrangement,and significantly fewer corpus lutea in the ovaries compared with the normal group(B1 group).The levels of serum LH,LH/FSH,and T were elevated(P<0.05).Conclusions Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can be used to successfully construct a non-obese PCOS rat model that possesses clinical characteristics.Subcutaneous injection of 60 mg/kg DHEA every 48 hours maintains the stability of the model.
9.A new alkaloid from Huperzia serrata and its biological activity
Xiao-ting QIAO ; Xin-xin CHENG ; Dan WANG ; Mei-han LAI ; Jia-qi WANG ; Xiao-min WANG ; Cai-lian RUAN ; Duo CAO
Acta Pharmaceutica Sinica 2024;59(12):3342-3346
The methanol extract of
10.Urban-rural differentials in the relationship between personality traits and changes in depressive symptoms.
Ting WANG ; Qiao Sheng LI ; Hao Ran LIU ; Wei Yan JIAN
Journal of Peking University(Health Sciences) 2023;55(3):385-391
OBJECTIVE:
The prevalence of depressive symptoms has become a significant public health issue in China. Research on the relationship between personality traits and changes in depressive symptoms, as well as further exploration of urban-rural differences, not only benefits for the understanding of the prevalence trend of depression in China, but also provides a useful reference for the government to develop personalized mental health prevention strategies.
METHODS:
Based on the data from the China Family Panel Studies in 2018 and 2020, a univariate analysis was conducted on 16 198 Chinese residents aged 18 years and above. Five dimensions of personality traits were conscientiousness, extraversion, agreeableness, neuroticism and openness. In the study, 16 198 residents were divided into "keep good group", "better group", "worse group" and "keep bad group" according to the changes in depressive symptoms in 2018 and 2020. After controlling for factors, such as gender and education, multinomial Logistic regression analysis was used to examine whether personality traits were associated with changes in depressive symptoms. In addition, we evaluated whether urban-rural and personality traits interacted to influence depressive symptoms.
RESULTS:
The five dimensions of personality traits were significantly correlated with changes in depressive symptoms. Conscientiousness, extroversion, and agreeableness were negatively associated with depressive symptoms, while neuroticism and openness were positively related. Urban and rural differences moderated the relationship between personality traits and depressive symptoms. Compared with urban residents, rural residents showed stronger correlations between neuroticism (OR=1.14; 95%CI: 1.00-1.30) and the group of depression-recovery, as well as conscientiousness (OR=0.79;95%CI: 0.68-0.93) and the group of persistent-depression.
CONCLUSION
The study finds that personality traits have a significant correlation with changes in depressive symptoms, with certain traits showing a negative or positive relationship. Specifically, higher levels of conscientiousness, extraversion, and agreeableness are associated with lower levels of depressive symptoms, while higher levels of neuroticism and openness are associated with higher levels of depressive symptoms. In addition, the study finds that rural residents have a stronger association between their personality traits and persistent or improved depressive symptoms, which highlights the need for tailoring mental health intervention and prevention programs that should take into account personality traits and urban-rural differences in China. By developing targeted strategies that are sensitive to personality differences and geographic disparities, policymakers and mental health professionals can help prevent and reduce the incidence of depressive symptoms, ultimately improving the overall well-being of Chinese adults. Meanwhile, additional studies in independent populations are needed to corroborate the findings of this study.
Adult
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Humans
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Personality
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Depression/etiology*
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China/epidemiology*
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Personality Inventory
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Surveys and Questionnaires


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