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.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

Heart failure is the leading cause of mortality in cardiovascular diseases and represents the ultimate common manifestation of most cardiovascular conditions,impacting over 60 million individuals globally.Currently,heart transplantation remains the standard treatment for heart failure patients.Adherence to fundamental pharmacotherapy can improve quality of life and extend survival time for heart failure patients.However,due to the complex mechanism of heart failure and numerous complications,the limitations of conventional heart failure treatment strategies in clinical work are gradually magnified.In recent years,interventional therapy has emerged as an innovative approach for managing heart failure,attracting significant attention and achieving substantial breakthroughs that offer new hope for affected individuals.Injectable hydrogel has garnered considerable interest in biomedicine due to its minimally invasive nature and capacity for efficient therapeutic drug delivery.In the context of chronic heart failure,injectable hydrogel finds application primarily in tissue regeneration,drug delivery,and immunotherapy.This review mainly describes the application and research progress of injectable hydrogel in the treatment of heart failure.

To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85％,12.88％,5.30％,3.79％,51.52％,and 6.06％,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9％(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.

Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.

The ezrin,radixin,moesin(ERM)protein family plays a pivotal role in cell morphology,migration,and signal transduction.Ezrin,as a prominent member of this family,is highly involved in these processes.Ezrin phosphorylation is particularly crucial,by regulating the interaction between ezrin and the actin cytoskeleton.This interaction is a key mediator of cytotoxicity in host cells infected with Helicobacter pylori,significantly impacting cell morphology.In this review,we comprehensively summarize the multifaceted role of ezrin protein in H.pylori-induced nodular gastritis.We consider the relationships between ezrin's structure,function,signaling pathways,and phosphorylation in the context of nodular gastritis.Moreover,this review highlights the role of ezrin protein as a potential therapeutic target,offering novel insights for the prevention and treatment of nodular gastritis.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Objective:To explore the clinical features of fatty liver disease (FLD) from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MASLD), so as to elucidate its clinical application value under three renames.Methods:Patients who were hospitalized in the Department of Hepatology, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, from January 2020 to September 2023 and met the diagnosis of NAFLD, metabolic-associated fatty liver disease (MAFLD), or MASLD were selected as the research subjects. The clinical indicators differences among the three groups of patients were compared, mainly including general information (age, gender, body mass index, past history, etc.), serological indicators (liver and kidney function, blood lipids, blood sugar, coagulation function, etc.), non-invasive liver fibrosis indicators, fat attenuation parameters, etc. Measurement data were analyzed using ANOVA and the rank sum test, while count data were analyzed using the χ2 test. Results:NAFLD, MAFLD, and MASLD prevalence rates among 536 cases were 64.0%, 93.7%, and 100%, respectively. 318 cases (59.3%) met the three fatty liver names at the same time among them. Male population proportions in NAFLD, MAFLD, and MASLD were 30.9%, 55.8%, and 53.9%, respectively. The alcohol consumption history proportion was 0, 36.7%, and 36.0%, respectively. The smoking history proportion was 7.0%, 31.9%, and 30.6%, respectively. The body mass index was (27.66 ± 3.97), (28.33 ± 3.63), and (27.90 ± 3.89) kg/m 2, respectively. The γ-glutamyltransferase levels were 26.6 (18.0, 47.0) U/L, 31.0 (20.0, 53.0) U/L, and 30.8 (19.8, 30.8) U/L, respectively. The high-density lipoprotein cholesterol levels were 1.07 (0.90, 1.23) mmol/L, 1.02 (0.86, 1.19) mmol/L, and 1.03 (0.87,1.21) mmol/L, respectively. Sequentially measured uric acid was (322.98 ± 84.51) μmol/L, (346.57 ± 89.49) μmol/L, and (344.89 ±89.67) μmol/L, respectively. Sequentially measured creatinine was 69.6 (62.9, 79.0) μmol/L, 73.0 (65.0, 83.5) μmol/L, and 73.0 (65.0, 83.0) μmol/L, respectively. The sequential analysis of obesity proportion was 74.3%, 81.7%, and 76.5%, respectively, with statistically significant differences ( P<0.05). Conclusion:Compared with the NAFLD population, the MAFLD and MASLD populations were predominantly male, obese, and had a history of smoking and drinking. The levels of γ-glutamyltransferase, uric acid, and creatinine were slightly higher, while the levels of high-density lipoprotein cholesterol were lower. MASLD appeared in NAFLD and MAFLD on the basis of inheritance and progression, emphasizing once again the important role of metabolic factors in a fatty liver.

Purpose/Significance To construct a specialized database for inflammatory demyelinating disease of the central nervous system(CNS),so as to contribute to clinical research and improve the diagnostic and treatment capabilities of primary healthcare institu-tions.Method/Process Using the internet to collect medical data,after processing and analysis,the CNS inflammatory demyelinating disease database is constructed.Using statistical analysis,natural language processing(NLP),artificial intelligence(AI)image recog-nition and data visualization and other technologies,the database information is integrated and analyzed.Result/Conclusion A standard-ized big database for CNS inflammatory demyelinating diseases is constructed,which enables visualization of clinical research data,pro-vides patient education and specialist training,and facilitates multi-center teleconsultations.The establishment of a specialized database for the CNS inflammatory demyelinating disease can promote the transformation of medical research achievements,provide references for future real-world clinical research,optimize the process of diagnosis and treatment,and improve the clinical capability of primary healthcare institutions.