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.Modified Ditan Tang Regulates Biorhythm-related Genes in Rat Model of Non-alcoholic Fatty Liver Disease
Zhiwen PANG ; Yu LIU ; Nan SONG ; Jie WANG ; Jingxuan ZHU ; Zhen HUA ; Yupeng PEI ; Qun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):115-124
ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop (TTFL) of biorhythm in the rat model of non-alcoholic fatty liver disease (NAFLD) and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank (n=20), model (n=15), and low-, medium-, and high-dose (2.68, 5.36, and 10.72 g·kg-1·d-1, respectively) modified Ditan tang (n=10) groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage, and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid (NEFA) assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining, and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 (BMAL1/ARNTL) in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1, circadian locomotor output cycles kaput (CLOCK), period circadian clock 2 (PER2), and cryptochrome1 (Cry1) in the hypothalamus and liver were determined by Real-time PCR and Western blot, respectively. ResultsCompared with the blank group, the model group showed elevated levels of TG, TC, LDL-C, AST, and ALT (P<0.01) and a lowered level of HDL-C (P<0.05) in the serum, elevated levels of TG and NEFA in the liver (P<0.01), pyknosis and deep staining of hypothalamic neuron cells, and a large number of vacuoles in the brain area. In addition, the model group showed lipid deposition in the liver, up-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.01), and down-regulated mRNA and protein levels of Cry1 and PER2 (P<0.01) in the hypothalamus and liver. Compared with the model group, all the three modified Ditan tang groups showed lowered levels of TG, TC, LDL-C, ALT, and AST (P<0.05, P<0.01) and an elevated level of HDL-C (P<0.05) in the serum, and lowered levels of TG and NEFA (P<0.05, P<0.01) in the liver. Furthermore, the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells, reduced lipid deposition in the liver, down-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.05, P<0.01), and up-regulated mRNA and protein levels of Cry1 and PER2 (P<0.05, P<0.01) in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK, BMAL1, Cry1, and PER2 in the TTFL of NAFLD rats.
3.Correlation between social jetlag and psychological behavior in upper primary school students
ZHAO Ruilan*, ZHU Guiyin, PENG Tao, ZHEN Guoxin, ZHAO Fangfang, SONG Qingqing, LI Li, MA Yinghua
Chinese Journal of School Health 2025;46(3):364-367
Objective:
To investigate the correlation between social jetlag and psychological behavior in upper primary school students,so as to provide reference for sleep health promotion in primary school students.
Methods:
From April to June 2024, a survey was conducted among 4 341 fourth and fifth grade students from 9 public primary schools in a district in Beijing. Sleep patterns were assessed using a self designed questionnaire, while psychological behavior was evaluated using the Strengths and Difficulties Questionnaire (SDQ)(parent version). A generalized estimating equation (GEE) model was used to examine the association between different levels of social jetlag and psychological behavior problem scores in primary school students.
Results:
The proportions of students with social jetlag of <1.0, 1.0-<2.0, and ≥2.0 h were 57.6%, 30.6%, and 11.8%, respectively. The GEE model analysis found that after adjusting for covariates, compared with primary school students with social jetlag of <1.0 h, those with 1.0 -<2.0 and ≥2.0 h had higher scores for internalizing behavior problems [ β (95% CI ) =0.23(0.05-0.41),0.28(0.02-0.54), P < 0.01]. Primary school students with ≥2.0 h of social jetlag had higher scores for externalizing behavior problems [ β (95% CI )=0.42 (0.13-0.71), P <0.01]. Among boys and primary school students with an average nighttime sleep duration of ≥9 h, comparied with social jetlag of <1.0 h,those with sucial jetlag 1.0-<2.0 h had higher scores on internalizing and externalizing behavior problems[ β (95% CI )=0.32(0.07-0.56),0.51 (0.11-0.90), 0.26 (0.06-0.46),0.58 (0.25-0.91), P <0.05].
Conclusions
Greater social jetlag may be a risk factor for internalizing and externalizing behavior problems in upper primary school students. Reducing social jetlag may help decrease the occurrence of psychological behavior problems in primary school students.
4.Predicting Postoperative Motor Function in High-risk Glioma Based on The Morphology Change of Motor Fiber Tracts
Qiang MA ; Song-Lin YU ; Chu-Yue ZHAO ; Xi-Jie WANG ; Song LIN ; Zhen-Tao ZUO ; Tao YU
Progress in Biochemistry and Biophysics 2025;52(4):1018-1026
ObjectiveGliomas in the motor functional area can damage the corticospinal tract (CST), leading to motor dysfunction. Currently, there is a lack of unified methods for evaluating the extent of CST damage, especially in patients with high surgical risk where the minimum distance from the lesion to the CST is less than 10 mm. This study aims to further clarify the classification method and clinical significance of CST morphological changes in these patients. MethodsThis retrospective study analyzed 109 high-risk functional area glioma patients who underwent neurosurgical treatment with preoperative diffusion tensor imaging (DTI) imaging and intraoperative neurostimulation guidance between 2014 and 2024. All patients had a lesion-to-tract distance (LTD) of less than 10 mm between the CST and the lesion. Preoperative DTI evaluation of CST involvement-induced morphological changes were reviewed. Patients were divided into 3 groups: 17 cases (15.6%) with symmetric CST morphology compared to the healthy side (CST symmetry), 48 cases (44.0%) with significant CST morphology changes compared to the healthy side (CST deformation), and 44 cases (40.4%) with CST overlap with the tumor (CST overlap). Then we classified patients according to preoperative assessment of tumor-induced morphological changes, and analyze postoperative motor function for each category. ResultsPostoperative pathology showed a significantly higher proportion of high-grade gliomas (HGG) in the CST overlap group compared to the other two groups (P=0.001). Logistic regression analysis showed that CST overlap was a predictor of HGG (P=0.000). The rate of total tumor resection in the CST deformation group and overlap group was lower than in the CST symmetric group (P=0.008). There was a total of 41 postoperative hemiplegic patients, with 4 cases (23.5%) in the CST symmetric group, 11 cases (22.9%) in the CST deformation group, and 26 cases (59.1%) in the CST overlap group. CST overlap with the tumor predicted postoperative hemiplegia (P=0.016). Two-way ANOVA analysis of the affected/healthy side and CST morphology groups showed significant main effects of CST grouping and healthy-affected side (P=0.017 and P=0.010), with no significant interaction (P=0.31). The fractional anisotropy (FA) value in the CST overlap group and the affected side was lower. A decrease in the FA value on the affected side predicted postoperative hemiplegia (sensitivity 69.2%, specificity 71.9%). ConclusionWe have established a method to predict postoperative hemiplegia in high-risk motor functional area glioma patients based on preoperative CST morphological changes. CST overlap leads to a decrease in CST FA values. This method can be used for precise patient management and aid in accurate preoperative surgical planning.
5.Advances in Cost Economics of Radiation Therapy and Thoracic Surgery for Early-Stage Lung Cancer
Zhen HUANG ; Lulu CHEN ; Qibin SONG
Cancer Research on Prevention and Treatment 2025;52(4):263-273
The cost economics of early-stage lung cancer treatments is a key focus in the field of lung cancer. The primary treatment modalities for early-stage lung cancer include radiotherapy and thoracic surgery, each offering distinct advantages in therapeutic outcomes and costs. To better understand the cost-effectiveness of radiotherapy versus thoracic surgery for early-stage lung cancer, this paper reviews the progress of recent research on economic evaluations of these two treatment approaches.
6.Joint effect of sitting posture habits and screen viewing distance on screening myopia among primary school students
ZHAO Ruilan, PENG Tao, ZHEN Guoxin, ZHAO Fangfang, LI Li, SONG Qingqing, ZHU Fan, MA Yinghua
Chinese Journal of School Health 2025;46(6):903-907
Objective:
To explore the association of screening myopia and sitting posture habits as well as screen viewing distance among primary school students, providing a scientific basis for myopia prevention and intervention among primary school students.
Methods:
From April to June 2024, a convenient sampling method was used to enroll 1 394 fourth grade students from four primary schools in a district of Beijing for vision examinations and questionnaire surveys. Logistic regression models were employed to analyze the relationship of screening myopia detection and sitting posture habits as well as viewing distance.
Results:
The screening myopia prevalence among primary school students was 63.8%. About 13.1% of students self reported poor sitting posture, and 47.1% selfreported a viewing distance of ≤20 cm. After adjusting for covariates including age, gender, school, sleep quality, parental myopia status, physical fitness level, daily high intensity physical activity, weekend outdoor activity time and types of after school services, Logistic regression analysis showed that students with poor sitting posture were more likely to have screening myopia than those with normal sitting posture ( OR =1.73,95% CI =1.03-2.92); students with a viewing distance of ≤20 cm were more likely to have screening myopia than those with a viewing distance of >20 cm( OR =1.32, 95% CI =1.02-1.71)( P <0.05). The association between sitting posture and screening myopia was more significant among boys( OR =2.00, 95% CI =1.03-3.88, P < 0.05 ). A multiplicative interaction was observed between sitting posture and viewing distance. Compared to primary school students with normal posture and a viewing distance of >20 cm, those with poor posture and a viewing distance of >20 cm were more likely to have screening myopia ( OR =1.82, 95% CI =1.12-2.96, P <0.05).
Conclusions
Both sitting posture habits and screen viewing distance are related to screening myopia in primary school students. Poor sitting posture poses a higher risk than screen distance, and the two factors exhibit an interactive effect on myopia risk.
7.Improvement effect and mechanism of sanguinarine on inflammatory pain in rats with lumbar disc herniation
Zhen RUAN ; Shenghua HE ; Xuehua GONG ; Song QIAO ; Chao WANG
China Pharmacy 2024;35(9):1087-1093
OBJECTIVE To study the improvement effect and mechanism of sanguinarine (SG) on inflammatory pain in rats with lumbar disc herniation (LDH) and its mechanism. METHODS LDH model rats were established and divided into model group, SG low-dose, medium-dose and high-dose groups (1.00, 2.50, 6.25 mg/kg), high-dose of SG+Anisomycin [mitogen-activated protein kinase (MAPK) activator] group (6.25 mg/kg SG+5 mg/kg Anisomycin), with 10 rats in each group. Another 10 rats were included as the control group. Each group was given corresponding drugs intraperitoneally, while the control group and model group were given an equal volume of normal saline intraperitoneally, once a day, for 7 consecutive days. The general situation and neurological changes of rats in each group were observed, and the pain threshold [including paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL)] of rats was determined; the histopathological changes of dorsal root ganglion (DRG) were observed in rats. The serum levels of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)] and pain factors [neuropeptide Y (NPY), 5-hydroxytryptamine (5-HT)] in rats were detected.The positive expressions of ionized-calcium binding adaptor molecule-1 (Iba-1) in spinal cord microglia and glial fibrillary acidic protein (GFAP) in astrocytes were observed. The expressions of proteins related to MAPK/extracellular signal-regulated kinase (ERK)/nuclear factor κB (NF-κB) signaling pathway, TNF-α and IL-1β proteins were detected in DRG tissue of rats. RESULTS Compared with the control group, the rats in the model group showed decreased appetite, hindlimb movement disorders, and disordered neuronal cell arrangement, the neurological score, the levels of TNF-α, IL-1β, NPY, the positive expressions of Iba-1 and GFAP, the phosphorylations of p38 MAPK, ERK1/2 and NF-κB p65, the protein expressions of TNF-α and IL-1β were significantly increased (P<0.05); PWMT, PWTL and the levels of 5-HT were significantly reduced (P<0.05). Compared with the model group, the rats of SG groups showed some relief in their mental appetite and hindlimb motor disorders, the intervertebral disc structure of DRG was restored, and the levels of the above quantitative indicators had significantly reversed (P<0.05). Anisomycin reversed the improvement effect of SG on inflammatory pain in LDH rats. CONCLUSIONS SG can improve inflammatory pain by inhibiting the activation of microglia in DRG tissue of LDH rats, reducing the release of inflammatory factors, and increasing pain threshold, and its mechanism of action may be related to the inhibition of MAPK/ERK/NF- κB signaling pathway.
8.Research progress in Fangfeng Tongsheng Powder
Cheng XU ; Zhen SONG ; Chongchao LI
International Journal of Traditional Chinese Medicine 2024;46(3):400-404
Fangfeng Tongsheng Powder has the effect of dispersing wind heat and internal purging heat. Returning to the origin of Liu Wansu's academic thought, it can be concluded that Fangfeng Tongsheng Powder should be based on the treatment of wind as the symptoms, the treatment of heat as the root, the treatment of both the symptoms and the root, and the double solution of the exterior and the interior. It should be set up for the syndrome of excessive heat and internal and external excess. In recent years, the basic and clinical research directions of this prescription in China mainly include skin diseases, endocrine and metabolic diseases, digestive system diseases, respiratory diseases, etc., while foreign related research focuses on obesity-related metabolic diseases. Studies have found that Fangfeng Tongsheng Powder has the effects of anti-allergy, regulating immunity and improving metabolic disorders. At present, the basic research on Fangfeng Tongsheng Powder in China is relatively insufficient, and the mechanism of Fangfeng Tongsheng Powder needs to be further explored, and more large samples and high-quality RCTs need to be carried out.
9.Adverse Reactions of Vaccine Vaccination in Children with Special Health Conditions in Kunming and Countermeasures
Zhen XU ; Yu LING ; Sixiang LIU ; Yu SONG ; Yang PENG ; Jingjing SUN
Journal of Kunming Medical University 2024;45(3):141-145
Objective To explore the occurrence of adverse reactions to vaccination in children with special health status in Kunming and the corresponding countermeasures.Methods The information data of 952 children with special health conditions who were vaccinated at the Child Healthcare Department of the Kunming Children's Hospital from October 2021 to February 2023 were collected,and descriptive methods were used for epidemiological analysis.Results The detection rate of adverse reactions in children with special health conditions in Kunming was 10.92%(104/952),all of which were mild adverse reactions.The top three vaccines with the highest detection rates of adverse reactions were adsorbed acellular pertussis-diphtheria-tetanus vaccine(Pertussis-Diphtheria-Tetanus),measles-mumps-rubella attenuated live vaccine(Measles-Mumps-Rubella),and meningococcal polysaccharide vaccine group A and C(Meningococcal A+C),with detection rates of 7.00%,4.14%,and 3.08%,respectively.The detection rate of adverse reactions in children with premature birth,allergy,and anemia after vaccination was higher,with detection rates of 13.87%,11.03%,and 10.05%,respectively.The detection rate of adverse reactions after more than two vaccinations was 73.08%,which was higher than the first vaccination detection rate of 26.92%.The clinical manifestations of vaccine adverse reactions were mainly fever,redness,and induration,with detection rates of 39.42%,21.15%,and 18.27%,respectively.The detection rate of adverse reactions in children with special health conditions under the age of two was higher,accounting for 75.00%.The detection rate of adverse reactions within 24 hours after vaccination was higher,accounting for 62.50%.After timely symptomatic treatment and follow-up observation,all adverse reactions in children with special health conditions after vaccination recovered within 7 days.Conclusion Adverse reactions after vaccination in children with special health conditions in Kunming are predominantly mild.The detection rate of adverse reactions post-vaccination for pertussis,measles,mumps,and meningococcal A+C is notably high.Children under 2 years old with premature birth,allergy,and anemia are more likely to have adverse reactions after vaccination.These adverse reactions typically manifest within 24 hours post-vaccination and resolve within 7 days.
10.Application of the OmniLogTM microbial identification system in the detection of the host spectrum for wild-type plague phage in Qinghai Plateau
Cun-Xiang LI ; Zhi-Zhen QI ; Qing-Wen ZHANG ; Hai-Hong ZHAO ; Long MA ; Pei-Song YOU ; Jian-Guo YANG ; Hai-Sheng WU ; Jian-Ping FENG
Chinese Journal of Zoonoses 2024;40(1):21-25
The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.


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