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.Environmental contamination status of norovirus outbreaks in schools and nurseries in Linhai City
ZHENG Jianjun, WANG Xi,HONG Danyang, LI Yaling, XU Qiumeng, ZHANG Huili, HAN Qian, LU Da, ZHENG Qiao
Chinese Journal of School Health 2025;46(4):601-603
Objective:
To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures.
Methods:
A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test.
Results:
Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05).
Conclusions
Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.
3.A Case of Hereditary Angioedema
Zusha QIAO ; Yan WANG ; Yanqing WANG ; Lu YANG ; Yan MA
JOURNAL OF RARE DISEASES 2025;4(3):331-333
A 43-year-old male patient presented with recurrent edema in different anatomical sites for over 10 years, with facial edema worsening 1 day prior to admission. He had been repeatedly admitted to dermatology, general surgery, and emergency departments of external hospitals due to " acute abdomen" and " laryngeal edema, " resistant to antihistamines and glucocorticoid therapy. Physical examination revealed non-pitting swelling of the right upper eyelid, bilateral cheeks, and lips asymmetrically. On the night of admission, he developed acute laryngeal edema with dyspnea, which was promptly treated, leading to clinical stabilization. Laboratory screening during the attack revealed decreased serum complement C4 levels, along with reduced functional activity and concentration of C1 esterase inhibitor, confirming a diagnosis of type 1 hereditary angioedema. The patient received lanadelumab for prophylaxis and achieved satisfactory clinical outcomes. He remains under long-term follow-up.
4.Effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test in screening for latent tuberculosis infection among HIV/AIDS patients
WANG Hui ; LI Jincheng ; LU Xing ; WANG Jinfu ; ZHU Limei ; LIU Qiao
Journal of Preventive Medicine 2024;36(7):639-643
Objective:
To evaluate the effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test (EC-ST) in screening for latent tuberculosis infection (LTBI) among HIV/AIDS patients, so as to provide insights into the applicability of EC-ST in LTBI screening among HIV/AIDS patients.
Methods:
From April to June 2023, HIV/AIDS patients under management and treatment in Yangzhou City, Jiangsu Province, were selected as study subjects. Basic information was collected through questionnaire surveys. LTBI was screened by EC-ST and interferon-gamma release assay (IGRA). Taking IGRA results as the diagnostic standard, the positive rate, sensitivity, specificity and consistency rate of EC-ST, and the impact of CD4+T lymphocyte (CD4) counts on the screening effect of EC-ST were analyzed.
Results:
A total of 523 HIV/AIDS patients were screened, including 458 males (87.57%) and 65 females (12.43%). The median age was 48.00 (interquartile range, 21.00) years. The positive rate of EC-ST was 7.27% and the positive rate of IGRA was 7.46%, with no statistically significant difference (P>0.05). The consistency rate of the two methods was 94.84%, and the Kappa value of 0.621 (95%CI: 0.489-0.752, P<0.05). The sensitivity of EC-ST was 64.10% and the specificity was 97.31%. Comparing the groups with CD4 counts <500 and ≥500 cells/μL, the consistency rates of the two methods were 95.32% and 94.44%, and the Kappa values were 0.568 and 0.650, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Comparing the groups with CD4 counts <200 and ≥200 cells/μL, the consistency rates of the two methods were 96.55% and 94.62%, and the Kappa values were 0.648 and 0.619, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05).
Conclusion
The effectiveness of EC-ST in screening for LTBI among HIV/AIDS patients is consistent with that of IGRA and is not affected by CD4 counts.
5.Value of evaluating Graves ophthalmopathy motiliny by MRI T2-mapping
Lu WANG ; Yao FAN ; Jian LONG ; Ming-Qiao ZHANG ; Chun LIU
Medical Journal of Chinese People's Liberation Army 2024;49(1):70-74
Objective To investigate the value of magnetic resonance imaging(MRI)T2-mapping in evaluating the activity of Graves ophthalmopathy(GO).Methods A total of 64 patients with GO in the Department of Endocrinology,the First Affiliated Hospital of Chongqing Medical University from July 2019 to January 2021 were collected.Simple random grouping was performed by computer,with 49 cases as observation subjects,and 15 patients for diagnostic test.According to clinical activity score(CAS),49 GO patients were divided into active group(CAS≥3 points,48 eyes)and inactive group(CAS<3 points,50 eyes).Normal control group(NC group)included 31 patients(62 eyes).All subjects underwent 3.0T orbital MRI T2-mapping.Measuring the T2 relaxation time(T2RT)of superior rectus,inferior rectus,medial rectus,and lateral rectus on five layers behind the eyeball on T2-mapping coronal images,and select the maximum value of T2RT in the five layers for each extraocular muscle to represent the T2RT of this extraocular muscle.Finally,select the maximum T2RT values of the four extraocular muscles,expressed as extraocular muscle maximum T2RT.Compare the differences of the above 5 indicators(superior rectus T2RT,inferior rectus T2RT,medial rectus T2RT,lateral rectus T2RT,extraocular muscle maximum T2RT)between active group,inactive group and NC group.ROC curve was used to analyze the diagnostic value of the above 5 indicators for GO activity assessment,and the diagnostic threshold was obtained.Then,another 15 GO patients were performed for diagnostic tests evaluation to determine the indicators of high diagnostic efficacy and the threshold of diagnostic activity.Results The T2RT of all extraocular muscles in active group were significantly higher than those in inactive group and NC group,the difference was statistically significant(P<0.001).The threshold value of the five indicators were obtained by ROC curve analysis.The maximum T2RT cut-off values of superior rectus muscle,inferior rectus muscle,medial rectus muscle,lateral rectus muscle and extraocular muscles for judging activity were 80.200 ms,97.045 ms,94.355 ms,85.750 ms and 101.385 ms respectively.Another 15 GO patients were performed for diagnostic tests,the indexes with relatively high sensitivity,specificity,positive predictive value and negative predictive value were inferior rectus T2RT and extraocular muscle maximum T2RT,the cut-off values of GO activity were 97.045 ms and 101.385 ms,respectively;the sensitivity were 91.7%and 93.8%,respectively;the specificity all were 80.0%.Conclusions MRI T2-mapping sequence has a good value in assessment of GO activity.The inferior rectus T2RT and extraocular muscle maximum T2RT can be choosed to evaluate the activity of GO.
6.Prognosis of 233 advanced renal cell carcinoma patients in Urumqi: a two-center study
Dilixiati DILIYAER ; Shuai YUAN ; Jiande LU ; Bingzhang QIAO ; Wenguang WANG ; Peng CHEN ; Rexiati MULATI ; Azhati BAIHETIYA
Journal of Modern Urology 2024;29(4):306-311
【Objective】 To investigate the clinical features, treatment methods and prognosis of advanced renal cell carcinoma (RCC) patients in Xinjiang, especially the Han population. 【Methods】 Clinical data of 233 patients with advanced RCC treated in The First Affiliated Hospital and The Affiliated Cancer Hospital of Xinjiang Medical University were retrospectively analyzed, including 133 Han patients.The median age of patients was 52 years (range: 23 to 87), and the maximum tumor diameter was (7.73±4.04) cm.Survival curves were plotted using the Kaplan-Meier method.Multivariate and univariate Cox regression analysis were conducted for all patients, and further analysis was performed for the Han patients. 【Results】 Among the 233 patients, 131 died during the average follow-up of 27.6 months (range: 1 to 120), and the median survival time was 12 months.In this cohort, 110 patients had lymph node metastasis, and 200 had distant metastasis, among them, 21 (10.5%) patients had brain metastasis and 45 (22.5%) patients had adrenal metastasis.The 1-, 3-, and 5-year survival rate were 48.9%, 18.3% and 6.1%, respectively.Univariate analysis revealed that International mRCC Database Consortium (IMDC) score, pathological type, lymph node metastasis, distant metastasis, number of metastatic foci and treatment methods impacted the prognosis in Xinjian (P<0.05).Multivariate analysis indicated that IMDC score, pathological type and distant metastasis were significant factors influencing the prognosis, which were also the prognostic factors of the Han patients (P<0.05). 【Conclusion】 In Xinjiang, patients with advanced renal cell carcinoma have a 6.1% 5-year survival rate and a median survival time of 12 months.Brain and adrenal metastases are common.Prognostic factors include IMDC score, pathological type, and distant metastasis for all patients, including the Han patients.
7.Meta-analysis of the myopia control effect of orthokeratology lenses with dif-ferent back optical zone diameters
Wenting WANG ; Lu QIAO ; Lemin CHEN ; Shaomin PENG
Recent Advances in Ophthalmology 2024;44(4):311-316
Objective To systematically evaluate the changes in axial length and treatment zone diameter among my-opic patients wearing orthokeratology lenses with different back optic zone diameters.Methods A comprehensive litera-ture search was conducted on PubMed,Embase,the Cochrane Library,Web of Science,Wangfang Med Online and CNKI databases in both Chinese and English to identify randomized controlled trials or controlled trials investigating orthokeratol-ogy lenses with varying back optical zone diameters.The literature was thoroughly reviewed by two researchers,who ex-tracted relevant data and conducted a methodological quality evaluation.Finally,meta-analysis was performed using Rev-Man 5.3 software.In all the included studies,orthokeratology lenses with a conventional back optic zone diameter were taken as the control group,while orthokeratology lenses with a reduced back optic zone diameter were utilized as the ex-perimental group.Results Eight studies involving 437 patients(459 eyes)with myopia were included.The results of me-ta-analysis showed that the axial length changes in the experimental group were significantly lower than those of the control group after wearing orthokeratology lenses for 6 months and 12 months(6 months:MD=-0.09,95%CI:-0.10 to-0.07,Z=10.50,P<0.05;12 months:MD=-0.11,95%CI:-0.13 to-0.09,Z=12.19,P<0.05);significant differ-ences in treatment zone diameter were observed between the experimental and control groups at various time points follow-ing orthokeratology lens wearing(MD=-0.82,95%CI:-1.04 to-0.59,Z=7.03,P<0.05).Conclusion Orthoker-atology lenses designed with smaller back optical zone diameters can effectively delay axial length growth in myopic pa-tients,but their long-term efficacy needs to be confirmed.
8.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
9.Establishment and evaluation of a neutralizing antibody detection model for West Nile virus pseudovirus
Wanlu ZHU ; Nan CHEN ; Xiangjun HAO ; Junjuan FENG ; Xing LU ; Jing WANG ; Guojiang CHEN ; Chunxia QIAO ; Xinying LI ; Chenghua LIU ; Beifen SHEN ; Jiannan FENG ; Jun ZHANG ; He XIAO
Chinese Journal of Experimental and Clinical Virology 2024;38(2):188-192
Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.
10.The current situation of willingness to receive prophylactic treatment among students with latent tuberculosis infection and its influencing factors in Jiangsu Province
WANG Zhan ; LI Zhongqi ; DING Xiaoyan ; LU Peng ; ZHU Limei ; LIU Qiao ; LU Wei
China Tropical Medicine 2024;24(3):244-
Objective To assess the willingness of students with latent tuberculosis infection (LTBI) in Jiangsu Province to undergo preventive treatment and identify factors influencing their decision, aiming to provide insights for tuberculosis prevention and control strategies in school. Methods The physical examination information of tuberculosis latent infection cases was collected from screenings of new school enrollment and contacts of tuberculosis patients in 6 cities of Jiangsu Province from December 2022 to December 2023. Data on past medical history and understanding of preventive treatment were gathered through an online questionnaire survey on the website of Juanxing, and the influencing factors related to the willingness to take preventive medication were analyzed by logistic regression analysis model. Results In December 2022 to December 2023, a total of 13 school tuberculosis outbreaks occurred in 6 cities, and 1 661 contacts were screened, among which 162 cases met the criteria for prophylactic medication, 96 cases were included in the study by filling in the questionnaire. A total of 22 600 new students from 56 schools participated in the TB screening upon enrollment, of which 358 tested positive for the tuberculin skin test alone, meeting the criteria for preventive medication, and 251 of them completed the willingness survey. Finally, 347 students who met the criteria for preventive treatment were included in the study, with 164 expressing to accept preventive treatment representing a treatment acceptance rate of 47.3%. The results of multivariate analysis showed that university (OR=17.950, 95%CI: 3.078-104.686, P=0.001) and contact with the source of school tuberculosis epidemic (OR=19.542, 95%CI: 6.289-60.726, P<0.001) were associated with increased willingness to receive preventive treatment, while unclear whether to pay for the drugs themselves (OR=0.349, 95%CI:0.133-0.916, P=0.032) was associated with decreased willingness to receive preventive treatment. Compared with Huai'an City, the willingness to receive preventive treatment was significantly lower among students from Nantong City (OR=0.005, 95%CI:0.000-0.063, P<0.001), Nanjing City (OR=0.022, 95%CI: 0.003-0.703, P<0.001) and Lianyungang City (OR=0.074, 95%CI:0.008-0.703, P=0.023). Conclusions The acceptance rate of preventive treatment among LTBI students in Jiangsu Province is not high and is affected by multiple factors. Health education and medication mobilization for preventive medication are essential.


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