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.

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

OBJECTIVES: To investigate the application value of thromboelastography (TEG) in assessing coagulation function in children with severe hemophilia A (HA) after emicizumab (EMI) therapy. METHODS: A retrospective analysis was performed on the activated partial thromboplastin time (APTT) and TEG testing results of 17 children with severe HA before and after EMI treatment at Shenzhen Children's Hospital from January 2023 to July 2024. Correlation analysis was conducted between coagulation factor VIII (FVIII) equivalent activity and reaction time (R value) measured by TEG. RESULTS: After EMI treatment, the mean bleeding rate for children with severe HA was 1.6 events per year, with 15 children (88%) without spontaneous bleeding or joint bleeding. The children with severe HA showed a significant reduction in APTT after EMI treatment (P<0.05), with a significantly shorter APTT than the normal control group (P<0.05). There was no correlation between APTT and FVIII equivalent activity after treatment (P>0.05). After EMI treatment, TEG parameters, including R value, kinetic time, alpha angle (α), maximum amplitude, clot strength, and coagulation index, shifted from a hypocoagulable state before treatment to a nearly normal state after treatment (P<0.05). The R value demonstrated a strong negative correlation with FVIII equivalent activity (r=-0.758, P<0.05). CONCLUSIONS The bleeding condition of children with severe HA can be effectively controlled after EMI treatment. Routine APTT testing cannot reflect true coagulation function, whereas TEG testing is clinically valuable in assessing the coagulation function of children with severe HA undergoing EMI treatment.
Humans ; Thrombelastography ; Hemophilia A/physiopathology* ; Male ; Child ; Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Blood Coagulation/drug effects* ; Child, Preschool ; Retrospective Studies ; Female ; Partial Thromboplastin Time ; Adolescent ; Infant

OBJECTIVE To investigate the changes in high performance liquid chromatography （HPLC） fingerprint spectra and nucleoside components between Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata， providing a reference for the quality evaluation of the latter. METHODS HPLC fingerprint was established for 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata following the Similarity Evaluation System of TCM Chromatographic Fingerprints （2012 Edition）. Hierarchical cluster analysis （HCA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS- DA） were conducted on their common peaks. The contents of four nucleoside components， hypoxanthine， uridine， adenine， and guanosine， in both Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were determined. RESULTS The similarity between the fingerprints of the 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， Succus bambusae pinella preparata， and their corresponding reference fingerprints ranged from 0.851 to 0.990. A total of 10 common peaks were obtained for both samples， and 4 components were identified as hypoxanthine， uridine， adenine， and guanosine. The results of HCA， PCA and OPLS-DA showed that the samples of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were clustered into separate categories， with OPLS-DA selecting 4 differential components between them， ranked by variable importance projection values as peak 8， peak 1， peak 6 （adenine） and peak 10. The content determination results showed that the average contents of hypoxanthine， uridine， adenine and guanosine in Succus bambusae pinella preparata declined by 15.90%， 12.00%， 26.04% and 22.18% compared to Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， respectively， with statistically significant differences in the contents of hypoxanthine， adenine and guanosine （P＜0.05 or P＜0.01）. CONCLUSIONS The established fingerprint and content determination methods are simple to operate and have good repeatability， which are suitable for qualitative and quantitative analysis of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata. The average contents of the four nucleoside components decreased after the processing of Succus bambusae pinella preparata.

This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m²·g^-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m²·g^-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.

Objective Human papillomavirus(HPV)is a detriment virus to human health,because it can cause malignant tumors.HPV vaccine has been developed and plays an important role in preventing a range of diseases caused by HPV.HPV vaccine as a primary prevention measure,has demonstrated excellent protective efficacy and safety in preventing HPV-related infection and cervical cancer.This article summarizes the application of preventive HPV vaccine and its safety,and provides reference for the widespread vaccination of HPV vaccine in China.

ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.

Tricuspid regurgitation(TR)is a common heart valve disease.According to the pathogenesis,TR can be divided into primary(organic)and secondary(functional)regurgitation,of which functional TR accounts for more than 90%.Patients with severe TR have poor prognosis and poor drug treatment,and surgery(valvuloplasty)is the main treatment.At present,transcatheter edge-to-edge tricuspid valve repair(T-TEER)has become an essential program of transcatheter treatment for TR,providing minimally invasive treatment for TR patients who cannot undergo surgery or are at high risk of surgery.T-TEER reduces the degree of regurgitation by clamping leaflets,and is currently in the early stage of research and development exploration and clinical validation,mainly for functional TR.T-TEER devices have also made significant progress(TriClip,PASCAL),and Chinese-made novel-designed T-TEER devices are also undergoing clinical trials(DragonFly-TTM,SQ-Kyrin-TTM,NeoBlazarTM).This paper reviews the current applications and research progress of T-TEER.

Objective To compare the changes of the Chinese Materia Medica resources(CMMR)in Sichuan based on the data of the 3rd Chinese Materia Medica Resource Inventory(CMMRI,1983-1986)and the 4th CMMRI(2011-2022).Methods Using new techniques,after field investigation,collection and identification of the specimens of the animals,plants and minerals.The data of the CMMR in Sichuan found in the 4th CMMRI were analysed and compared with the data of 3rd CMMRI.Results ①9055 species of CMMR were found in Sichuan during the 4th CMMRI,including 8272 species of medicinal plants,745 species of medicinal animals and 38 species of medicinal minerals.Compared with the 3rd CMMRI,the number of CMMR found in Sichuan have greatly increased.The number of medicinal plants increased 5018 species,the number of medicinal animals increased 637 species and the number of medicinal minerals increased 5 species,too.②The medicinal plants is the main part of the CMMR,and the higher plants(7774 species)has the absolute advantage of the CMMR.The top 20 families which have plenty of plant species include Compositae,Rosaceae,Leguminosae,Ranunculaceae,etc.③ Based on the data of the CMMR of the 183 counties in Sichuan,the reserves of 235 species of wild CMMR in Sichuan is about 36.72 million ton.There were 49 CMMR which have reserves beyond 100 thousand tons,such as Arisaematis rhizoma,Epimedii folium,Cimicifugae rhizoma,Acori tatarinowii rhizoma,Gentianae macrophyllae radix,Polygoni multiflori radix etc.④In 2021,there were 215 species of CMMR cultivated in Sichuan,the main species were Aurantii fructus,Chuanxiong rhizoma,Polygonati rhizome,Salviae miltiorrhizae radix et rhizome.The planting area was 8.17 million and the production was 1.26 million ton.⑤All 183 countries were found CMMR,the number of the species of CMMR in 30 countries exceeded 800,including 16 countries which had more than 1000 kinds of CMMR,such as Emeishan,Hongya,Muli etc.The total types of the CMMR(up 118.31%),the reserves of the wild CMMR(up 119 times)and the number of the counties(up 3 times)which had plenty of CMMR,showed a marked increase over the 3rd CMMRI.8 new species were found in the the 4th CMMRI,such as Codonopsis atriplicifolia,Tongoloa tagongensis,Allium xinlongense,etc.Conclusion The species,the reserves of the CMMR and the resource rich countries in Sichuan are the top 3 in China and Sichuan is worthy of the title of"Hometown of Traditional Chinese Medicine".The compositions and types of the family,genus and species of the CMMR in Sichuan have significantly increased.The basic information of the CMR in Sichuan was clearly found out during the 4th CMMRI,and beneficial for the sustainable development and utilization of the CMMR in Sichuan.

Objective:To investigate the etiology of hand, foot and mouth disease (HFMD) in Mianyang city in 2022, and to analyze the genetic characteristics of coxsackievirus A6.Methods:Pharyngeal swabs were collected from patients with HFMD in Mianyang city in 2022. Real-time fluorescence quantitative PCR was used to detect enteroviruses in the samples. Part of the VP1 gene in enterovirus-positive samples was amplified by nested PCR using enterovirus typing primers to further identify the viral types. The VP1 coding region of all CVA6-positive samples and the whole genome of some samples were amplified and sequenced by PCR. The endemic strain in Mianyang city was analyzed for phylogeny, gene homology, amino acid variation and genetic recombination.Results:A total of 151 pharyngeal swabs were collected, and 104 enterovirus-positive samples were detected by real-time fluorescence quantitative PCR, with an overall detection rate of 68.88% (104/151). The typing results showed that there were 77 cases of CVA6 infection, with a positive rate of 50.99% (77/151). The full-length VP1 genes of 77 CVA6 strains were amplified, sequenced, and successfully spliced, and phylogenetic analysis showed that all 77 strains were of the D3 genotype. There were multiple amino acid variant sites in the prevalent strains in Mianyang city compared with the reference strain. Twenty whole genome sequences were amplified, sequenced, and successfully spliced, and homology analysis showed that the nucleotide homology between the 20 positive sequences ranged from 97.0% to 99.9%. Phylogenetic tree and recombination analysis showed that no recombination occurred in the coding regions of the epidemic strains in this study.Conclusions:The predominant pathogen causing HFMD in Mianyang city in 2022 is CVA6 D3 subtype, which is consistent with the national epidemic in 2022.