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.Investigation on a suspected outbreak of carbapenem-resistant Acinetobacter baumannii nosocomial infection in an intensive care unit
Mei HUANG ; Xiaobo GUI ; Ya YANG ; Feng LU ; Juanxiu QIN ; Yan LI ; Shuyi ZHANG ; Wenqin ZHOU ; Xiaofang FU ; Haiqun BAN
Shanghai Journal of Preventive Medicine 2024;36(5):435-438
ObjectiveTo investigate a suspected outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) nosocomial infection in an intensive care unit (ICU) and provide scientific evidence for prevention and control of multi-drug resistant nosocomial infection. MethodsClinical and epidemiological data of 4 patients with CRAB infection were retrospectively investigated in the ICU of Renji Hospital in November 2021. Environmental hygiene monitoring and multilocus sequence typing (MLST) were conducted and intervention measures were taken. ResultsA total of 4 cases with CRAB infection were identified, among which 1 case was determined to be community-acquired and3 cases were hospital-acquired. The isolated strains shared the same drug resistance, and were all classified into ST368 type. In the surface and hand samples (n=40), 2 CRAB strains were detected in the air filter beside the bed of the first case, with a detection rate of 5%. After adopting comprehensive prevention and control strategies, including environmental cleaning and disinfection, hand hygiene, staff management and training, and supervision, no similar case with CRAB infection was found. ConclusionThis suspected outbreak of CRAB nosocomial infection may be induced by inadequate environmental cleaning and disinfection, and inadequate implementation of hand hygiene. Timely identification, investigation, and targeted measures remain crucial to effective control of possible nosocomial infection.
3.A Study on Brain Functional Connectivity in Patients With Disorders of Consciousness Based on Auditory Stimulation
Ning YIN ; Fan YANG ; Zhong-Zhen LI ; Ya-Mei HAN ; Ji-Cheng LI ; Gui-Zhi XU
Progress in Biochemistry and Biophysics 2024;51(6):1434-1444
Objective At present, the grading evaluation of patients with disorders of consciousness (DOC) is still a focus and difficulty in related fields. Electroencephalogram (EEG) can directly read and continuously reflect scalp electrical activity generated by brain tissue structure, with high temporal resolution. Auditory stimulation is easy to operate and has broad application prospects in clinical detection of DOC. The causal network can intuitively reflect the direction of information transmission through the causal relationship between time series, helping us better understand the information interaction between different regions of the brain of patients. This paper combines EEG and causal networks to explore the differences in brain functional connectivity between patients with unresponsive arousal syndrome (VS) and those with minimum state of consciousness (MCS) under auditory stimulation. MethodsA total of 23 DOC patients were included, including 11 MCS patients and 12 VS patients. Based on the Oddball paradigm, auditory naming stimulation was performed on DOC patients and EEG signals of DOC patients were synchronously collected. The brain functional networks were constructed using multivariate Granger causality method, and the differences in node degree, clustering coefficient, global efficiency, and causal flow of the brain networks between MCS patients and VS patients were calculated. The differences in network characteristics of patients with different levels of consciousness under auditory stimulation were compared from the perspective of cooperation between brain regions. ResultsThe causal connectivity between most brain regions in MCS patients was stronger than that in VS patients, and MCS patients had more brain network connectivity edges than VS patients. The average degree (P<0.05), average clustering coefficient, and global efficiency (P<0.05) of MCS patients under naming stimulation were higher than those of VS patients. The difference in out-degree between each node of VS patients was larger, and the difference in in-degree between each node of MCS patients was smaller. The difference in in-degree of MCS patients was more significant than that of VS patients, and the inflow and outflow of information in the brain functional network of MCS patients were stronger than those of VS patients. MCS and VS patients had differences of causal flow in the frontal and temporal lobes, the direction of information transmission in the parietal lobe and central region was not the same, and MCS patients had more electrodes as causal sources than VS patients. ConclusionThe information transmission ability of MCS patients is stronger than that of VS patients under auditory naming stimulation. Compared with VS patients, MCS patients have an increase in the number of electrode channels as the causal source, an increase in information output to other brain regions, and also an increase in the information output within brain regions, which may indicate a better state of consciousness in patients. MCS patients have more electrode channels for information output in the frontal lobe than VS patients, and the number of electrode channels for changing the direction of information transmission in the frontal lobe is the highest. The frontal lobe is closely related to the level of consciousness in patients with consciousness disorders. This study can provide a theoretical basis for the grading evaluation of consciousness levels in DOC patients.
4.Study on the inhibitory effect of pachymaric acid on the inflammatory response of intestinal epithelial cells induced by Fusobacterium nucleatum and its mechanism
The Chinese Journal of Clinical Pharmacology 2024;40(4):544-548
Objective To investigate the effect of pachymic acid(PA)on HIEC-6 inflammatory response of intestinal epithelial cells infected by Fusobacterium nucleatum(Fn)and its possible mechanism.Methods HIEC-6 cells were divided into control group,model group(1× 108 CFU·mL-1 Fn infection),experimental-L group(1× 108 CFU·mL-1 Fn+2 μmol·L-1 PA),experimental-M group(1× 108CFU·mL-1 Fn+4 μmol·L-1 PA),experimental-H group(1× 108 CFU·mL-1 Fn+8 μmol·L-1 PA),pcDNA-TLR4 group(1 × 108 CFU·mL-1 Fn+8 μmol·L-1 PA+transfected pcDNA-TLR4).After 12 h of treatment,the cell proliferation was detected by cell counting kit-8(CCK-8)test and Edu test respectively.The expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay(ELISA)and real-time quantitative polymerase chain reaction(RT-qPCR)respectively.The apoptosis was detected by flow cytometry.Western blot assay was used to detect the expression level of cell related proteins.Results The apoptosis rates of control,model,experimental-L,experimental-M,experimental-H and pcDNA-TLR4 groups were(3.51±0.31)%,(23.38±1.85)%,(16.74±0.54)%,(12.10±1.44)%,(8.89±0.63)%and(14.87±0.88)%,respectively;IL-8 content were(23.25±1.41),(79.69±4.37),(68.94±2.63),(51.46±2.56),(34.18±2.63)and(71.09±5.08)pg·mL-1,respectively;IL-1β contents were(8.81±0.49),(51.65±2.13),(35.98±3.47),(24.83±2.47),(14.79±1.25)and(43.89±1.59)pg·mL-1.Compared between model group and control group,compared between experimental-L,experimental-M,experimental-H groups and model group,compared between pcDNA-TLR4 group and experimental-H group,the differences of the above indexes were all statistically significant(all P<0.05).Conclusion Pachymaric acid may improve the apoptosis of Fn infected intestinal epithelial cells by inhibiting TLR4/NF-κB pathway and inflammatory response.
5.Clinical trial of bevacizumab combined with paclitaxel and carboplatin in the treatment patients with of recurrent/metastatic cervical cancer
Yang XIANG ; Jin-Long CAO ; Gui-Mei NIE ; Ying LI ; Yan-Ying SUN ; Shu WANG ; Ping-Rong XIE
The Chinese Journal of Clinical Pharmacology 2024;40(8):1121-1125
Objective To analyze the efficacy of bevacizumab combined with paclitaxel+carboplatin in the treatment of recurrent/metastatic cervical cancer,and to explore the influence on survival prognosis of patients.Methods Patients with recurrent/metastatic cervical cancer were divided into control group and treatment group according to different treatment methods.The control group received paclitaxel combined with carboplatin chemotherapy regimen(intravenous infusion of 170 mg·m-2 paclitaxel and carboplatin(AUC=5 mg·mL-1·min)for 3 weeks as a course of chemotherapy),and the treatment group was given bevacizumab on the basis of control group,intravenous infusion of 15 mg·kg-1 bevacizumab,once every 3 weeks.Both groups were treated for 3 cycles of treatment by taking 3 weeks as 1 treatment cycle.The clinical efficacy,levels of serum tumor markers,quality of life,survival prognosis and occurrence of drug-related adverse reactions during treatment were compared between the two groups.Results There were 41 cases in treatment group and 48 cases in control group.After treatment,the overall response rate(ORR)of treatment group and control group were 31.71%(13 cases/41 cases)and 14.58%(7 cases/48 cases),with no statistical significance(P>0.05).After treatment,the disease control rate(DCR)in control group and treatment group were 62.50%(30 cases/48 cases)and 82.93%(34 cases/41 cases);the squamous cell carcinoma antigen(SCCA)levels were(3.58±0.73)and(2.52±0.57)ng·mL-1;carbohydrate antigen 19-9(CA19-9)levels were(23.60±4.29)and(19.19±3.72)U·mL-1;carbohydrate antigen 15-3(CA15-3)levels were(27.13±5.36)and(22.86±3.94)U·mL-1;carbohydrate antigen 125(CA125)levels were(39.24±6.88)and(26.47±5.09)U·mL-1;the overall improvement rates of quality of life were 41.67%(20 cases/48 cases)and 73.17%(30 cases/41 cases),the progression-free survival times were 8.67 months(95%CI:7.82-9.53)and 10.25 months(95%CI:9.68-10.81),the total survival times were 9.96 months(95%CI:9.13-10.79)and 11.47 months(95%CI:11.00-11.93),all with significant difference(all P<0.05).There were no statistically significant differences in the incidence of nausea and vomiting,leukopenia,thrombocytopenia and liver-kidney function impairment between both groups(all P>0.05).Conclusion Bevacizumab combined with chemotherapy has significant efficacy in the treatment of recurrent/metastatic cervical cancer,and it can reduce the levels of serum tumor markers,enhance the quality of life,and improve the survival prognosis,and it has good safety.
6.Antibacterial activity of turmeric (Curcuma longa L ) extract and effect on bacterial cell membranes
Lu HAN ; Chao ZHOU ; Xiu-fang BI ; Mei-gui HUANG ; Gang HAO
Acta Pharmaceutica Sinica 2024;59(8):2265-2272
In the present study, the antibacterial spectrum of turmeric extract was analyzed by measuring the minimum inhibitory concentration (MIC), and the antibacterial mechanism of turmeric extract was elaborated by determining its effects on the permeability and integrity of the cytoplasmic membrane, energy metabolism, and the morphology of the tested bacteria (
7.Design and implementation of medical alliance nursing collaborative management system based on block chain
Mei-Gui CHEN ; Xu XU ; Xiao-Ping ZHU ; Xiong CHEN ; Qiao-Mei SHANG
Chinese Medical Equipment Journal 2024;45(3):47-55
Objective To design a medical alliance nursing collaborative management system based on block chain to provide technical support for nursing collaborative management.Methods A medical alliance system was designed based on the five-layer technical architecture of consortium blockchain,which used Linux system for establishing a Fabric development environment and network configuration,smart contract and Java language software development kit for realizing user interface operation,Bootstrap and Jquery technologies for constructing the front-end Web interface,Spring Boot for constructing the back-end interface.There were five functional modules for consortium blockchain member management,business management,data storage and sharing,patient medical record management and platform supervision involved in the system,which were developed with the technologies of encryption algorithm,hash operation,smart contract,consensus mechanism and etc.Results The system developed contributed to improving the mechanism for quality nursing resource sinking and continuous nursing care,reconfiguring the point incentive mechanism,promoting the collaborative development of nursing symbiotic network and enabling multi-node interactions to form a synergistic synergy.Conclusion The system developed conforms to the development trend of integrated care service of medical alliance,enhances the core competitiveness of nursing care and provides references for formulating blockchain solutions applicable to medical alliance scenarios.[Chinese Medical Equipment Journal,2024,45(3):47-55]
8.Building and validating a risk prediction model for malnutrition during concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma
Ting CHENG ; Jia-Mei LU ; Ting-Ting HUANG ; Xiao-Jun HUANG ; Gui-Rong YANG ; Wei LI ; Rong-Sa WEI ; Li-Na WEI ; Yan-Xin ZHANG ; Jie-Ying LIU
Parenteral & Enteral Nutrition 2024;31(2):73-82
Objective:To develop and validate a model to predict the risk of malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. Methods:From April 2022 to August 2023, 430 patients with nasopharyngeal carcinoma who were admitted to the department of radiotherapy of the first affiliated hospital of Guangxi medical university in Nanning were conveniently selected as the study subjects, and they were divided into the modelling group (300 cases) and the internal validation group (130 cases) in the internal validation group in the ratio of 7:3, and 61 patients with nasopharyngeal carcinoma admitted to the affiliated cancer hospital of Guangxi medical university in Nanning City were selected as the external validation group. Logistic regression was used to establish the risk prediction model and draw nomograms,Hosmer-Lemeshow, calibration curve and ROC were used to verify the goodness of fit and predictive power of the model, and clinical decision curve was used to assess the clinical utility. Results:Logistic regression analysis showed that skeletal muscle mass index, self-rated anxiety scale score, Pittsburgh sleep quality questionnaire score, Chinese diet pagoda score, regular exercise, and digestive symptom groups were the influencing factors for malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. In the modelling group, the area under the ROC curve was 0.853 (95%CI:0.81 ~ 0.89), the maximum Youden was 0.600, and the corresponding specificity was 0.764 and the sensitivity was 0.836. The Hosmer-Lemeshow test=4.040 and P=0.853 indicated that the model had good predictive ability. Calibration curve of the calibration showed that the predictive effect of the model matched actual probability well, with an average absolute error was 0.024. When the threshold probability of the clinical decision curve is 0.05 ~ 0.85, the clinical response rate is higher. The area under the operating curve of the subjects in the internal validation group was 0.891, the sensitivity was 77.36%, the specificity was 89.61%, and the practical application accuracy was 84.62%. The area under the operating curve of the subjects in the external validation group was 0.886, the sensitivity was 76.00%, the specificity was 83.33%, and the overall accuracy was 80.33%. Conclusion:The risk prediction model constructed in this study has a good effect, which can effectively predict the incidence of malnutrition in patients receiving concurrent radiotherapy and chemotherapy for nasopharyngeal carcinoma, and provide a reference for clinical staff to formulate and implement nutritional interventions.
9.Clinical Observation of Acupuncture Combined with Acupoint Catgut Embedding Therapy on Back-Shu and Front-Mu Points and External Application on Shenque Point for Premature Ovarian Failure
Xue-Juan ZHAO ; Hong-Wei YANG ; Xiu-Ming LIU ; Rui-Yang SHEN ; Mei-Xia WEI ; Gui-Yun TAN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(11):2906-2911
Objective To observe the clinical efficacy of acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque(RN8)point for premature ovarian failure(POF).Methods A total of 62 patients with POF were randomly divided into the observation group and the control group,with 31 patients in each group.The observation group was treated with acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque point,and the control group was treated with hormone replacement therapy.After three months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the traditional Chinese medicine(TCM)syndrome scores,as well as the ovarian volume,number of antral follicle,and antral follicle diameter of the patients in the two groups before and after treatment were observed.The changes of serum follicle stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)levels before and after treatment were compared between the two groups.Results(1)The total effective rate was 93.55%(29/31)in the observation group and 80.64%(25/31)in the control group.The efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the serum FSH,LH and E2 levels of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with statistically significant differences(P<0.05).(3)After treatment,ovarian volume,number of antral follicle,and antral follicle diameter were significantly improved in the two groups(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,and the difference was statistically significant(P<0.05).Conclusion The treatment of POF with acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque point can significantly improve the clinical symptoms of the patients,conducive to the recovery of ovarian function,and significantly improve the sex hormone levels of the patients,with precise clinical efficacy.
10.Treatment Strategies and Research Ideas of Acupuncture for Emotional Disorder in Perimenopause
Mei GENG ; Lin-Ling OUYANG ; Xiao-Kang XU ; Gui-Zhen CHEN ; Yun-Xiang XU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(11):2912-2917
Perimenopause is a vulnerable stage for emotional disorders such as anxiety and depression,which is the result of a combination of bio-psycho-social factors,and it seriously affect the quality of life of perimenopausal women.Therefore,finding safe and effective treatments is one of the urgent problems in modern medicine.This paper summarises the etiology and treatment of emotional disorder in perimenopause in Chinese and western medicine,and on this basis,this paper discusses the clinical diagnostic and treatment strategies and research ideas of acupuncture in treating emotional disorder in perimenopause,thus providing a new idea for the prevention and treatment of emotional disorder in perimenopause.

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