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.Analysis of risk factors for piracetam-associated thrombocytopenia and the establishment of risk prediction model
Tianmin HUANG ; Xingming LU ; Mei ZHENG ; Guizong GUO ; Xin LU ; Yilin LUO ; Yingxia YANG
China Pharmacy 2025;36(10):1226-1231
OBJECTIVE To analyze the risk factors contributing to piracetam-associated thrombocytopenia and develop a predictive model for risk prediction. METHODS The electronic medical record information of inpatients treated with piracetam was collected retrospectively from the First Affiliated Hospital of Guangxi Medical University from January 2021 to December 2023, including gender, age, underlying diseases, combined medication, and laboratory data, etc. Patients were divided into the occurrence group and the non-occurrence group according to whether thrombocytopenia occurred, and the differences in clinical data between the two groups were compared. The independent risk factors were determined through univariate/multivariate Logistic regression analysis. A nomogram was drawn to visually present the independent risk factors, and a risk prediction model was constructed. The predictive efficacy of the model was evaluated using the receiver operating characteristic (ROC) curve, Bootstrap internal validation and calibration curve. RESULTS A total of 224 patients were included, among which 196 cases were in the non- occurrence group and 28 cases in the occurrence group. The incidence of thrombocytopenia was 12.50%. The results of the univariate Logistic regression analysis showed that the proportion of patients using three or more combined antibiotics and the level of serum creatinine in the occurrence group were significantly higher than those in the non-occurrence group, while the level of hemoglobin was significantly lower (P<0.05). The results of the multivariate Logistic regression analysis revealed that the use of three or more combined antibiotics, low hemoglobin level and high serum creatinine level were independent risk factors for piracetam-associated thrombocytopenia (P<0.05). The constructed risk prediction model was LogitP= -1.114+1.256×three or more combined antibiotics-0.017×hemoglobin level+0.009×serum creatinine level. The AUC of the ROC curve of this model was 0.757, and the optimal cut-off value was 0.474; the AUC of the ROC curve of the Bootstrap internal validation was 0.733; the apparent curve and the bias-corrected curve were close to the ideal curve. CONCLUSIONS The use of three or more antibiotics, along with low hemoglobin level and high serum creatinine level, are identified as independent risk factors for piracetam-associated thrombocytopenia. The developed risk prediction model demonstrates good predictive value.
3.Association between medium to long term ambient PM 2.5 exposure and overweight/obesity among primary and secondary school students
Chinese Journal of School Health 2025;46(7):937-940
Objective:
To investigate the association between medium to long term PM 2.5 exposure around school areas and overweight/obesity among primary and secondary school students in Guangxi, providing data support and theoretical foundations for scientifically addressing overweight and obesity in primary and secondary school students.
Methods:
From September to November 2023, a stratified cluster random sampling method was employed to select 251 183 students aged 7-18 years (grade 1 to grade 12) from 14 prefecture level cities (111 districts and counties) in Guangxi. PM 2.5 mass concentration data were obtained from the Tracking Air Pollution in China (TAP) dataset. Preliminary comparative analysis was conducted using the Mann-Whitney U test, while binary Logistic regression models were applied to quantify the relationship between PM 2.5 exposure and overweight/obesity. Restricted cubic spline analysis was further utilized to examine the nonlinear association between PM 2.5 concentration and overweight/obesity risk.
Results:
The detection rate of overweight/obesity among Guangxi students in 2023 was 19.5%. The median PM 2.5 concentration in the year prior to the study was higher in the overweight/obesity group (23.22 μg/m 3) compared to the non overweight/obesity group (22.63 μg/m 3) ( Z=-15.66, P <0.01), and consistent trends were observed across gender (male/female) and educational stage (primary/junior/senior high school) subgroups (all P <0.01). Binary Logistic regression revealed that for every 10 μg/m 3 increase in the annual average PM 2.5 concentration, the risk of overweight/obesity increased by 12% ( OR=1.12, 95%CI=1.09- 1.15 , P <0.01). Restricted cubic spline analysis indicated a nonlinear relationship between monthly PM 2.5 levels and overweight/obesity risk ( P trend <0.01). Below 22.68 μg/m 3, PM 2.5 exposure showed no significant association with obesity risk; above the threshold, the risk increased with rising PM 2.5 levels.
Conclusion
Medium to long term PM 2.5 exposure around school environments is significantly associated with overweight/obesity among primary and secondary school students.
4.Evidence-based study on postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor
Xiandan LUO ; Yanli LU ; Yihang WU ; Yanxiang GUO ; Xiaoyi YAN ; Yongchao HUO ; Hui YAN ; Zhenjiang YANG ; Hongliang ZHANG
China Pharmacy 2025;36(18):2328-2333
OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed, Embase, Web of Science, CBM, VIP, Chinese Medical Journal Data, Wanfang Data, and CNKI, as well as the official websites of GIN, NICE, Medlive, AHRQ, CSCO, ASCO, and NCCN. The search period was from the establishment of the databases/websites to March 10, 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows: scope and purpose of 85.07%, participants of 47.92%, rigor of development of 57.49%, clarity of presentation of 88.02%, applicability of 8.20%, and independence of 53.39%. Among them, 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants, rigor of development, and independence of the guidelines/consensuses in China were significantly lower than foreign countries (P<0.05); the scores for participants and rigor of development of the guidelines were significantly higher than consensuses (P<0.05). The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients;platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients; non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants, rigor of development, and independence, to recommend treatment plans based on the different stages of ovarian cancer, and develop guidelines/consensuses that align with China’s national conditions.
5.Analysis of current radiation protection and occupational health management in non-medical institutions in Hebei Province, China, 2022
Dawei GUO ; Yuan SUN ; Yingnan LUO ; Jingzhan ZHANG ; Yanwen YANG ; Kaijian ZHOU
Chinese Journal of Radiological Health 2024;33(1):74-79
Objective To investigate the number, distribution, and types of radiation of non-medical radiation institutions in Hebei Province, China, and to explore the current radiation protection in the employing units and occupational health management of radiation workers in 2022. Methods A questionnaire survey was conducted in the non-medical institutions engaged in nuclear technology application in Hebei Province, and different types of employing units were selected to monitor the radioactivity level in the workplace. Results A total of 681 non-medical institutions engaged in radiation technology application completed the survey, covering all cities with subordinate districts in the province, including 1605 radioactive devices, 2960 active devices, 45 non-uranium metal mines, and 14 non-sealed workplaces. A total of 8617 radiation workers were surveyed, with a personal dose monitoring rate of 70.9%, a radiation protection training rate of 61.1%, and an occupational health examination rate for radiation workers of 59.3%. A total of 614 radiation protection monitoring instruments were provided, with a personal protective equipment allocation rate of 51.1% and a personal dose alarm device allocation rate of 51.8%. The radiation occupational hazardous factor testing was completed for 54 workplaces, and the results were all qualified. Conclusion There are still significant deficiencies in personal dose monitoring in the radiation work units in non-medical institutions and occupational health examination in the radiation work units in our province. The health administrative departments should strengthen health supervision and law enforcement, enhance radiation protection and skill training for employers, and more effectively control the impact of radiation hazards on personnel health.
6.Biological Basis of Premature Ejaculation Based on Theory of "Brain-heart-kidney-semen Chamber" Axis
Dongyue MA ; Anmin WANG ; Jiutian YANG ; Dicheng LUO ; Ziwei ZHAO ; Jun GUO ; Fu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):203-209
The theory of "brain-heart-kidney-semen chamber" axis is proposed based on the basic theories of traditional Chinese medicine, the modern physiological characteristics of men's diseases, and clinical practice. According to this theory, dysfunctions of the brain, heart, kidney, and semen chamber are the core mechanisms for the occurrence of premature ejaculation, and the loss of control of the opening and closing of the seminal orifices due to the dysfunction of the semen chamber is the final link in the occurrence of premature ejaculation. The treatment of premature ejaculation based on the theory of "brain-heart-kidney-essence chamber" axis highlights the overall regulation of the Zang-fu organs involved in the disease, while focusing on the simultaneous treatment of the mind and body. By exploring the biological basis of the "brain-heart-kidney-essence chamber" axis and premature ejaculation, we propose that the biological basis of premature ejaculation and the axis is mainly related to the function decline of the local brain area, neuromodulation malfunction, central neurotransmitter imbalance, endocrine disorders, and enhanced sensory afferents of the penis. This study aims at providing a new approach for the prevention and treatment of premature ejaculation by traditional Chinese medicine and a scientific basis for the development of more effective therapeutic methods.
7.Effects of Maxing Shigan Decoction on IL-6/STAT3 Signaling Pathway and TRPV1 Receptor in Rats with Cough Variant Asthma
Qian YANG ; Bo JIANG ; Qin-Guo SUN ; Kun LYU ; Meng LUO ; Tian-Hui HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):729-735
Objective To investigate the therapeutic effects and mechanisms of Maxing Shigan Decoction on cough variant asthma(CVA)rats.Methods Sixty rats were randomly divided into normal group,model group,low and high dose groups of Maxing Shigan Decoction,and high-dose of Maxing Shigan Decoction + signal transducer and activator of transcription 3(STAT3)activator Colivelin(Col)group,12 rats in each group.Except for the normal group,the CVA model was constructed by intraperitoneal injection of ovalbumin combined with moxa fumigation in all other groups of rats.After the corresponding treatment,the rats were observed for signs and cough counts,airway resistance(RE)was detected by pulmonary function meter,eosinophils(EOS)were counted by Diff-Quik staining,histopathological features of the lungs and bronchial tubes were observed by hematoxylin-eosin(HE)staining method,and the lung tissues were detected by enzyme-linked immunosorbent assay(ELISA)for monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α),and the protein expression levels of interleukin 6(IL-6),STAT3,and transient receptor potential vanilloid-1 channel(TRPV1)were detected by Western Blot.Results Compared with the normal group,rats in the model group showed obvious asthma symptoms,severe inflammatory cell infiltration was seen in the lung tissue,bronchial epithelial cell necrosis,ciliated adhesion,mucus,and RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,TRPV1 were elevated(P<0.05);compared with the model group,rats in the low-and high-dose groups of Maxing Shigan Decoction showed significant improvement in asthma symptoms,reduction in lung and bronchial injury,and dose-dependent reduction in RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P<0.05);compared with the high-dose group of Maxing Shigan Decoction,the rats in the high-dose Maxing Shigan Decoction+Col group showed increased asthma,increased lung and bronchial injury,and increased RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P<0.05).Conclusion Maxing Shigan Decoction can effectively improve cough variant asthma in rats,and its mechanism is related to the inhibition of IL-6/STAT3 signaling pathway and the high expression of TRPV1.
8.CT features of Chlamydia psittaci pneumonia
Dengfa YANG ; Yuwen GUO ; Ting YANG ; Jianhua CHEN ; Xiaoqin XU ; Jianhua LUO
China Modern Doctor 2024;62(8):30-32
Objective To investigate CT features of Chlamydia psittaci(C.psittaci)pneumonia patients.Methods Ten patients with C.psittaci pneumonia were collected retrospectively based on macro gene second-generation sequencing(mNGS).The radiological manifestations of the disease were analyzed.Results Seven patients(70%)had contact history with birds(poultry)or their feces.Chest CT on the day of admission was mainly mass patchy consolidation,all of which were located in single lung,involving 8 cases(80%)with one lobe and 2 cases(20%)with two lobes.All of them were accompanied by air bronchogram,9 cases(90%)with ground glass shadow and 8 cases(80%)with interstitial changes.One case(10%)showed a reversed halo sign,and 1 case(10%)showed fan-shaped consolidation.Nine cases(90%)showed progress with increased fusion or new lesions within nine days.Conclusion CT findings of C.psittaci pneumonia have certain characteristics,and combining with history of contacting birds(poultry)can suggest diagnosis.
9.Correlation between geriatric nutritional risk index and adverse events in elderly hemodialysis patients
Zhihua SHI ; Yidan GUO ; Pengpeng YE ; Chunxia ZHANG ; Xiaoling ZHOU ; Meng JIA ; Xiyou ZHANG ; Yang LUO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(1):42-45
Objective To explore the relationship between geriatric nutritional risk index(GNRI)and adverse outcomes in elderly patients undergoing maintenance hemodialysis(MHD).Methods A prospective cohort trial was conducted on 337 MHD patients aged ≥60 years in hemodialysis centers of 11 hospitals in Beijing from April to June 2017.Their baseline data were collected,and they were divided into non-malnutrition(GNRI≥98,226 cases),mild malnutrition(92≤GNRI<98,81 cases),and major malnutrition groups(GNRI<92,30 cases).All of them were followed up until June 2018.The endpoint events were all-cause mortality and cardiovascular disease(CVD)mortality.Kaplan-Meier survival analysis was used to compare the cumulative survival rate among the 3 groups.Multivariate Cox regression model was employed to analyze the relationship of GNRI with all-cause and CVD mortality.Results The mild and major malnutrition groups had significantly lower BMI,serum albumin level and GNRI(P<0.01).During the median follow-up of 52(4.4-52.0)weeks,56(16.6%)patients died of all-cause death and 25(44.6%)of CVD death.Kaplan-Meier survival curve showed significant differences in all-cause mortality(x2=30.484,P<0.01)and CVD mortality(x2=22.398,P<0.01)in the 3 groups.Multivariate Cox regression analysis indicated that,as a continuous variable,elevated GNRI was a protective factor for all-cause mortality(HR=0.910,95%CI:0.870-0.952,P=0.000)and CVD mortality(HR=0.895,95%CI:0.852-0.940,P=0.000),and as a categorical variable,mild and major malnutri-tion were independently correlated with all-cause and CVD mortality(P<0.05).Conclusion GNRI is an independent risk factor for all-cause and CVD mortality in elderly MHD patients.Mo-nitoring the nutritional status using GNRI can predict the risk of adverse prognosis.
10.Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2024;14(1):86-99
A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.


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