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.

Objective To analyze the current situation of the knowledge-attitude-practice among noise-exposed workers at an airport apron. Methods A total of 494 noise-exposed workers from an airport apron were selected as the study subjects using the judgmental sampling method. A self-designed "Occupational Protection Knowledge, Attitudes, and Practices Questionnaire" was used to assess the current situation of knowledge-attitude-practice on occupational protection. Results Regarding the awareness of noise hazards among the study subjects, the awareness rates of noise-induced impairment on digestive function and reproductive system were the lowest (44.9% and 37.7%, respectively). The awareness rate of noise-induced negative emotions increased with length of service (P<0.01). Regarding the occupational protection knowledge for noise, the awareness rate of occupational noise-induced deafness was “incurable” was the lowest (39.1%). The support rate for five kinds of occupational protection attitudes for noise was generally >85.0%, while only 58.3% of the study subjects consistently or frequently wearing earplugs during work. The most common source of noise hazard and protection knowledge was pre-employment training (76.9%), followed by occupational disease prevention and control campaigns (76.1%). Conclusion Noise-exposed workers in this airport apron have incomplete awareness of non-auditory system hazards caused by noise, and the awareness of knowledge of some occupational protection is relatively low. Although their attitudes toward occupational protection are positive, many workers still fail to consistently wear personal protective equipment at work.

[摘 要] 目的：探讨miR-7-5p调控叉头框转录因子M1（FOXM1）对食管鳞状细胞癌（ESCC）KYSE-150细胞增殖、凋亡和免疫逃逸的影响。方法：通过双萤光素酶报告基因实验验证miR-7-5p与FOXM1的靶向结合位点。收集2022年1月至2024年10月期间苏州大学附属常州老年病医院收治的56例ESCC患者的癌组织和癌旁组织标本，以及患者的基本临床资料。采用qRT-PCR法检测ESCC组织中miR-7-5p和FOXM1的表达水平，分析其表达与临床病理特征的关系。常规培养的KYSE-150细胞为Ctrl组，用Lipofectamine 3000转染试剂将质粒转染KYSE-150细胞，分为Mimic NC组、miR-7-5p mimic组、miR-7-5p mimic + OE-NC组和miR-7-5p mimic + OE-FOXM1组。EdU染色和CCK-8实验检测KYSE-150细胞增殖能力，流式细胞术检测KYSE-150细胞的凋亡和CD8+ T细胞凋亡情况，WB法检测KYSE-150细胞中PD-L1、FOXM1、BAX和PCNA蛋白的表达。构建KYSE-150细胞裸鼠移植瘤模型，观察miR-7-5p过表达对移植瘤生长和组织中Ki-67、FOXM1表达的影响。结果：miR-7-5p可以靶向负调控FOXM1（P < 0.05）。ESCC组织中miR-7-5p呈低表达，FOXM1呈高表达（均P < 0.05），其表达分别与TNM分期、分化程度显著相关联（均P < 0.05）。miR-7-5p过表达组EdU阳性细胞率、细胞增殖能力、CD8＋ T细胞凋亡率，以及PD-L1、PCNA、FOXM1 mRNA和蛋白均显著降低（均P < 0.05），细胞凋亡率、miR-7-5p、BAX水平均显著升高（均P < 0.05）；同时过表达FOXM1则可逆转上述作用（均P < 0.05）。miR-7-5p过表达可降低小鼠移植瘤质量和体积，以及移植瘤组织中Ki-67、FOXM1蛋白的表达（均P < 0.05）。结论：miR-7-5p过表达能够显著抑制KYSE-150细胞增殖和免疫逃逸并促进细胞凋亡，其机制可能是通过靶向负调控FOXM1基因实现的。

Objective To investigate the effects of trifluridine-tipiracil hydrochloride tablets(TAS-102)combined with oxaliplatin(L-OHP)on proliferation,migration,invasion and apoptosis of hepatocellular carcinoma SNU-449 cells and its possible mechanism.Methods SNU-449 cells were divided into control group(without drugs),TAS-102 group(2 μg·mL-1),oxaliplatin group(1.2 μg·mL-1)and combination group(2 μg·mL-1 TAS-102+1.2 μg·mL-1 L-OHP).Cell counting kit-8 assay was used to detect cell proliferation ability;Transwell assay was used to detect cell migration and invasion;the apoptosis rate was analyzed by flow cytometry;the expressions of B-cell lymphoma-2(Bcl-2),Bel-2-associated X(Bax),E-cadherin and Vimentin were detected using Western blotting.Results Survival rate of cells in control group,TAS-102 group,oxaliplatin group and combination group were(100.00±2.98)％,(80.26±5.55)％,(78.49±5.76)％and(47.82±4.26)％,respectively;the number of cell migration were 436.83±27.50,228.17±15.87,171.67±19.49 and 113.83±11.34,respectively;the number of cell invasion were 332.67±19.95,205.33±13.65,219.67±14.49 and 116.83±11.30,respectively;the apoptosis rates were(2.32±0.07)％,(6.74±0.24)％,(6.37±0.18)％and(10.67±0.41)％,respectively;the relative expression levels of Bax protein were 0.28±0.01,0.53±0.03,0.75±0.03 and 1.11±0.03,respectively;the relative expression levels of Bel-2 protein were 0.65±0.03,0.32±0.02,0.23±0.02 and 0.13±0.01,respectively;the relative expression levels of E-cadherin were 0.15±0.01,0.24±0.02,0.35±0.02 and 0.64±0.02,respectively;the relative expression levels of Vimentin were 0.65±0.03,0.27±0.01,0.34±0.02 and 0.18±0.01,respectively.Comparison of each treatment group with the control group and comparison of the combination group with monotherapy group,the above indexes were statistically significant(all P＜0.05).Conclusion The synergistic effect of TAS-102 and oxaliplatin enhanced the inhibitionon proliferation,migration,and invasion,and promoted cell apoptosis of SNU-449 cells,and the mechanism may be related to the promotion of Bax and E-cadherin proteins and the inhibition of Bel-2 and Vimentin proteins.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Tympanosclerosis is the hyaline degeneration and calcium deposition of the lamina propria of tympanic membrane and the submucosa of middle ear under long-term chronic inflammatory stimulation. At present, treatment primarily involves the surgical removal of sclerotic foci and reconstruction of auditory ossicular chain. However, excision of sclerotic lesions near critical structures like the facial nerve canal and vestibular window may result in complications like facial paralysis, vertigo, and sensorineural hearing loss. Developing safer and more effective treatments for tympanosclerosis has become an international research focus. Recent years have seen novel explorations in the treatment of tympanosclerosis. Therefore, this article reviews the latest advancements in research on the treatment of tympanosclerosis.
Humans ; Tympanoplasty ; Ear, Middle ; Ear Ossicles/surgery* ; Tympanic Membrane/surgery* ; Tympanosclerosis

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

UDP glycosyltransferase (UGT) is a terminal modifying enzyme for the formation of flavonoid glycosides. In this study, we obtained two glycosyltransferase genes, CtUGT25 and CtUGT18, which are closely related to the synthesis of safflower flavonoids, through the Pierce correlation analysis of the expression of glycosyltransferase genes in the safflower corolla transcriptome database at different developmental stages with the contents of the major constituents of safflower metabolome database, and bioinformatically analyzed the gene and protein sequences of the two genes. Expression pattern analysis revealed that CtUGT25 was mainly expressed in the corolla, with the highest expression on day 3 of flowering stage; CtUGT18 was mainly expressed in the root, with the highest expression on day 1 of flowering stage. Functional validation was verified in safflower by Agrobacterium-mediated pollen-tube pathway transgenesis method, demonstrating that CtUGT25 promoted the accumulation of kaempferol-3-O-glucoside and hydroxysafflor yellow A (HSYA), and CtUGT18 promoted the accumulation of kaempferol-3-O-glucoside and orientin, both of which may be the glycosyl-modifying enzymes for the synthesis of safflower flavonoids. Meanwhile, in vitro experiments demonstrated the catalytic activity of CtUGT25 protein on naringenin, quercetin, apigenin, kaempferol, luteoin, 2-hydroxynaringenin and galangin. This study serves as reference for future advancements in regulating the quality of safflower using molecular biotechnology, particularly focuses on the industrial production of safflower exclusive component HSYA. Additionally, it offers valuable insights for researching related genes in other plants.

It has gradually become a consensus in the industry that the traditional Chinese medicine gypsum should be decocted first, but the understanding of decocting method is not completely unified in the works of doctors since ancient times, and there are occasional disputes about whether it is necessary to decocting first. In this study, the phase determination, physical and chemical characterization, qualitative and quantitative analysis of inorganic and organic components of the decoctions of herbal pairs and the whole prescription Maxingshigan decoction with gypsum as the center, and the pre-decoctions and co-decoctions of them were carried out to explore the scientific connotation of the pre-decoctions of gypsum. Results show that decoction phases were different between the co-decoctions and pre-decoctions of licorice-gypsum (Gancao-Shigao, GC-SG), ephedra-gypsum (Mahuang-Shigao, MH-SG) and almond-gypsum (Xingren-Shigao, XR-SG). The results of the micromorphology, particle size and zeta potential of herbal pairs and prescription (Quanfang, QF) showed that the supramolecular particles in pre-decoctions were smaller, more uniform and more stable than the co-decoctions. The results of organic components analysis showed that different cooking methods did not change the organic composition and content. ICP-OES results showed that the content of inorganic components in pre-decoctions was higher than in co-decoctions for the same boiling time of gypsum. The IR results showed that the pre-decoctions had stronger chemical functional group effect than the co-decoctions. To sum up, compared with the co-decoction, the pre-decoction of gypsum has different phase state and chemical composition interaction, and the difference of inorganic composition is an important material basis affecting the change of phase state compared with the co-decoction. It indicates that the material basis of traditional Chinese medicine decoction is indeed different whether gypsum is decocted first or not, which can provide a basis for the clinical application of decocted gypsum.