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.Evaluation of life cycle management system on patients'prognosis after transcatheter aortic valve replacement
Ruo-Yun LIU ; Ran LIU ; Mei-Fang DAI ; Yue-Miao JIAO ; Yang LI ; San-Shuai CHANG ; Ye XU ; Zhi-Nan LU ; Li ZHAO ; Cheng-Qian YIN ; Guang-Yuan SONG
Chinese Journal of Interventional Cardiology 2024;32(6):311-316
Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9%vs.17.7%,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P<0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95%CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.
3.Event-related potential study on vigilant attention in children with sleep disordered breathing
Ye HE ; Huijie HAN ; Ming FA ; Chaoqun WANG ; Haitian MEI ; Fangqiao ZHAO ; Yang YI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(6):500-504
Objective:To explore the vigilant attention function and behavioral changes in sleep disordered breathing(SDB) children.Methods:Thirty SDB children (SDB group) and 30 normal children (control group) were selected from June 2022 to August 2023. All participants underwent continuous performance test(CPT-AX) (Go/Nogo) and behavioral test. The latency and amplitude of contingent negative variation(CNV) components under cue/uncue conditions in leads F3, Fz and F4 were measured. The t-test and Mann-Whitney U test were used to conduct statistical analysis by SPSS 25.0 software. Results:(1) There were no statistically significant differences in the number of correct responses, reaction time and number of false alarms between the SDB group and the control group (all P>0.05).(2) The latencies of cue-CNV in the SDB group(F3: 618.00(582.50, 644.50)ms, Fz: 603.00(579.50, 634.00)ms, F4: (606.87±25.07)ms) were longer than those in the control group(F3: (508.47±25.82)ms, Fz: 502.00(470.00, 520.50)ms, F4: 514.00(487.00, 536.50)ms) in leads F3, Fz and F4. The latency of cue-CNV of lead F4 in the SDB group was higher than that in the control group, and the difference was statistically significant ( P<0.05). The latencies of uncue-CNV in lead F3 and Fz in the SDB group were higher than those in the control group, and the differences were statistically significant (both P<0.05). Conclusion:SDB children have shown activation in the right brain area during attentional tasks, and the prolonged CNV latency may be a sensitive neuroelectrophysiological marker for early clinical assessment of vigilant attention dysfunction.
4.Event-related potential study on attentional cognitive function in children with different subtypes of sleep disordered breathing
Huijie HAN ; Chaoqun WANG ; Haitian MEI ; Jiuming GAO ; Ye HE ; Fangqiao ZHAO ; Yang YI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(10):883-889
Objective:To explore the cognitive function characteristics of children with primary snoring (PS) and obstructive sleep apnea-hypopnea syndrome (OSAHS) using event-related potentials.Methods:From October 2020 to October 2022, 20 children with OSAHS, 20 children with PS, and 22 normal children were recruited for continuous performance task (CPT) and behavioral assessments. ERP and behavioral data were meticulously recorded, with measurements of N1, P2, N2, and P3 wave amplitudes and latencies at F3, Fz, and F4 electrode sites. Statistical analyses were conducted using one-way ANOVA and Kruskal-Wallis test via SPSS 25.0 software.Results:(1) Behavioural test: There was no statistically significant difference in terms of correct responses, response times, and false alarms among the three groups (all P>0.05). (2) F3 Lead: There were statistically significant differences in Go-P2 amplitude, Nogo-P2 amplitude, Nogo-P2 latency, Go-P3 amplitude, and Nogo-P3 latency among the three groups (all P<0.05). Specifically, the OSAHS group exhibited higher Go-P2 amplitude((15.03±5.12) μV vs (10.97±5.50)μV), Nogo-P2 amplitude((14.80±5.84) μV vs (9.67±4.79)μV), and Go-P3 amplitude((11.58±6.02) μV vs (7.49±4.89) μV) compared to the normal group. Additionally, the OSAHS and PS groups exhibited longer Nogo-P2 latency compared to the normal group((223.10±20.61) ms vs (208.00±23.09) ms, (230.60±13.61) ms vs (208.00±23.09) ms), as well as prolonged Nogo-P3 latency((459.20±34.26) ms vs (460.40±24.52) ms and (429.91±31.49) ms) (all P<0.05). Fz Lead: There were statistically significant differences in Go-N1, Go-P2, Nogo-P2, Go-P3, Nogo-N2 wave amplitudes, and Nogo-P3 latency among the three groups (all P<0.05). Compared to the normal group, the OSAHS group exhibited increased Go-P3 amplitude((9.07±5.68) μV vs (5.10±3.51) μV) and decreased Nogo-N2 amplitude((-8.80±5.97) μV vs (-12.84±4.86) μV). Moreover, both the OSAHS and PS groups had prolonged Nogo-P3 latency compared to the normal group((481.60±45.16) ms vs (435.13±28.17) ms and 484.00(443.50, 525.00) ms vs (435.13±28.17) ms) (both P<0.05). F4 Lead: There were statistically significant differences in Go-P2 and Nogo-P2 wave amplitudes among the three groups (all P<0.05). Compared to the normal group, the OSAHS group demonstrated increased Go-P2 amplitude((13.72±5.64) μV vs (9.70±4.59) μV) and Nogo-P2 amplitude((13.90±5.35) μV vs (9.64±3.74) μV) (both P<0.05). Conclusions:Both children with OSAHS and PS exhibit attentional cognitive impairments. However, children with OSAHS demonstrate more pronounced deficits in conflict monitoring, response inhibition, and executive functioning. The prolonged latency of the P3 wave serves as a sensitive electrophysiological marker for the early detection of neurocognitive impairment in children with sleep disordered breathing.
5.On-site rapid detection of multiple pesticide residues in tea leaves by lateral flow immunoassay
Gao JUNXIA ; Zhang TIANYI ; Fang YIHUA ; Zhao YING ; Yang MEI ; Zhao LI ; Li YE ; Huang JUN ; Zhu GUONIAN ; Guo YIRONG
Journal of Pharmaceutical Analysis 2024;14(2):276-283
The application of pesticides(mostly insecticides and fungicides)during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea.Thus,it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits.However,the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues.In this study,nine types of lateral flow immunochromatographic strips(LFICSs)were developed to detect the pesticides of interest(fenpropathrin,chlorpyrifos,imidacloprid,thiamethoxam,acet-amiprid,carbendazim,chlorothalonil,pyraclostrobin,and iprodione).To reduce the interference of tea substrates on the assay sensitivity,the pretreatment conditions for tea samples,including the extraction solvent,extraction time,and purification agent,were optimized for the simultaneous detection of these pesticides.The entire testing procedure(including pretreatment and detection)could be completed within 30 min.The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.
6.Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas:a multicenter clinical research protocol
Bi ZE ; Jin GAO ; Xiao-Fen ZHAO ; Yang-Fang LI ; Tie-Song ZHANG ; Xiao-Mei LIU ; Hui MAO ; Ming-Cai QIN ; Yi ZHANG ; Yong-Li YANG ; Chun-Ye HE ; Yan ZHAO ; Kun DU ; Lin LIU ; Wen-Hao ZHOU ; Chinese High Altitude Neonatal Medicine Alliance
Chinese Journal of Contemporary Pediatrics 2024;26(4):403-409
Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]
7.Clinical characteristics and nutritional status of children with Crohn's disease and risk factors for malnutrition
Dong-Dan LI ; Xiao-Lin YE ; Mei-Chen WANG ; Hong-Mei HUANG ; Jie YAN ; Tian-Zhuo ZHANG ; Fei-Hong YU ; De-Xiu GUAN ; Wen-Li YANG ; Lu-Lu XIA ; Jie WU
Chinese Journal of Contemporary Pediatrics 2024;26(11):1194-1201
Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6%) and 50 girls (42.4%),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7%,87/118),diarrhea (37.3%,44/118),and hematochezia (32.2%,38/118),and 63.6% (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6% (75/118),and the children with moderate or severe malnutrition accounted for 67% (50/75). There were 50 children (42.4%) with emaciation,8 (6.8%) with growth retardation,and 9 (7.6%) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3%),anemia in 74 children (62.7%),and a reduction in 25 hydroxyvitamin D in 15 children (60%,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.
8.Research progress on environmental DNA detection and geographical origin inference in forensic science
Qi YANG ; Kelai KANG ; Hongcheng MEI ; Jiajin PENG ; Jiahui YUAN ; Yaosen FENG ; Jian YE ; Anquan JI ; Le WANG
Chinese Journal of Forensic Medicine 2024;39(3):349-356
The geographical origin of forensic evidence provides important information for crime investigation and solving cases,and is one of the key elements of criminal cases.Previous studies have shown significant differences in the distribution of microorganisms in different regions.Detecting environmental DNA samples and inferring the geographical and spatial sources can provide clues and evidence for case handling.However,due to the diversity of criminal environments and the trace amount of frequently encountered exhibits,stable and reliable technical methods for inferring geographical origin from environmental DNA are not yet available.This article summarizes the sample collection and DNA extraction methods for four types of environmental samples:dust,soil,water,and air.It compares the differences between amplicon sequencing and metagenomic sequencing in studying environmental biological populations,outlines the full process of high-throughput sequencing-based data analysis,and focuses on reviewing the research progress in inferring geographical sources of environmental samples based on bacteria,fungi,and other eukaryotes,to provide references for establishing sequencing and analysis methods for environmental DNA in forensic DNA laboratories and exploring environmental DNA information for forensic applications.
9.Application of artificial intelligence in ophthalmic plastic surgery
Yingge MA ; Shixu LI ; Yongxin ZHANG ; Jun MEI ; Lin YE ; Meina YANG
International Eye Science 2024;24(3):453-457
The advancement of computers and data explosion have ushered in the third wave of artificial intelligence(AI). AI is an interdisciplinary field that encompasses new ideas, new theories, and new technologies, etc. AI has brought convenience to ophthalmology application and promoted its intelligent, precise, and minimally invasive development. At present, AI has been widely applied in various fields of ophthalmology, especially in oculoplastic surgery. AI has made rapid progress in image detection, facial recognition, etc., and its performance and accuracy have even surpassed humans in some aspects. This article reviews the relevant research and applications of AI in oculoplastic surgery, including ptosis, single eyelid, pouch, eyelid mass, and exophthalmos, and discusses the challenges and opportunities faced by AI in oculoplastic surgery, and provides prospects for its future development, aiming to provide new ideas for the development of AI in oculoplastic surgery.
10.Research on Satisfaction Degree of Doctor-patient Communication Quality based on Patient Perception
Yang FU ; Yi SUN ; Lishan LI ; Ye ZHENG ; Yunqi ZHANG ; Lei SHI ; Mei YIN
Chinese Medical Ethics 2024;35(4):374-379
Objective sampling method was used to conduct a questionnaire survey on outpatients in two hospitals in Guangdong province in order to evaluate patients’ satisfaction with the quality of medical service. This paper explored the factors that affect patients’ evaluation of medical service quality, and found that patients’ age was negatively correlated with the evaluation of medical service quality. It is suggested that the establishment of friendly medical institutions should be carried out according to the national policy. At the same time, the management mechanism of hospital should be improved, the number of medical service centers for "efficient" should be increased, and the medical service personnel should be regularly trained; carry out medical knowledge education in community, improve the popularization of personal medical knowledge and close the cognitive gap between doctors and patients.

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