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.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of P. grandiflorum under climate change. The results showed that the model simulation effect was the best when the Maxent parameter was FC (feature combination) = LQPH (L: linear features; Q: quadratic features; P: product features; H: hinge features) and RM (regularization multiplier) = 2.1, AUC (area under curve) = 0.901, and the model prediction showed that P. grandiflorum was widely distributed in 28 provinces of China under the current climate conditions, with a suitable area of 2 337 419.98 km². Under the influence of climate change in the future, the area of suitable habitat of P. grandiflorum showed a decreasing trend, and the distribution center as a whole showed a trend of northward and eastward shift. The distribution area of P. grandiflorum in the three main producing areas is affected by climate change, and the overall trend is that the future suitable distribution area of Chifeng in Inner Mongolia increases, while the future suitable distribution area of Zibo in Shandong and Taihe, Bozhou in Anhui decreases or even disappears under the SSP5-8.5 scenario (shared socioeconomic pathways). It is suggested to maintain and protect the ecological environment and germplasm resources of the reserved area suitable for the growth of P. grandiflorum, and increase the cultivation research in the expansion area of P. grandiflorum, so as to lay a foundation for the subsequent expansion of P. grandiflorum planting and to promote the protection and sustainable development of P. grandiflorum resources.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

italic>Fusarium oxysporum widely exists in farmland soil and is one of the main pathogenic fungi of root rot, which seriously affects the growth and development of plants and often causes serious losses of cash crops. In order to screen out natural compounds that inhibit the activity of Fusarium oxysporum more economically and efficiently, random forest, support vector machine and artificial neural network based on machine learning algorithms were constructed using the information of known inhibitory compounds in ChEMBL database in this study. And the antibacterial activity of the screened drugs was verified thereafter. The results showed that the prediction accuracy of the three models reached 77.58%, 83.03% and 81.21%, respectively. Based on the inhibition experiment, the best inhibition effect (MIC = 0.312 5 mg·mL^-1) of ononin was verified. The virtual screening method proposed in this study provides ideas for the development and creation of new pesticides derived from natural products, and the screened ononin is expected to be a potential lead compound for the development of novel inhibitors of Fusarium oxysporum.

OBJECTIVES: To explore the relationship between atherogenic index of plasma (AIP) and childhood asthma. METHODS: This retrospective study included 86 children with asthma admitted to the Changzhou Second People's Hospital Affiliated to Nanjing Medical University from July 2020 to August 2022 as the asthma group and 149 healthy children undergoing physical examination during the same period as the control group. Metabolic parameters including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and blood glucose, as well as general information of the children such as height, weight, body mass index, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, and feeding history, were collected. Multivariable logistic regression analysis was used to study the relationship between AIP, triglycerides, and high-density lipoprotein cholesterol and asthma. The value of AIP, triglycerides, and high-density lipoprotein cholesterol for predicting asthma was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: The AIP and triglyceride levels in the asthma group were significantly higher than those in the control group, while high-density lipoprotein cholesterol was significantly lower (P<0.05). However, there was no significant difference in total cholesterol and low-density lipoprotein cholesterol between the two groups (P>0.05). Before and after adjusting for height, weight, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, feeding method, and blood glucose, multivariable logistic regression analysis showed that AIP, triglycerides, and high-density lipoprotein cholesterol were associated with asthma (P<0.05). ROC curve analysis showed that the optimal cutoff value for predicting asthma with AIP was -0.333, with a sensitivity of 80.2%, specificity of 55.0%, positive predictive value of 50.71%, and negative predictive value of 82.85%. The area under the curve (AUC) for AIP in predicting asthma was significantly higher than that for triglycerides (P=0.009), but there was no significant difference in AUC between AIP and high-density lipoprotein cholesterol (P=0.686). CONCLUSIONS AIP, triglycerides, and high-density lipoprotein cholesterol are all associated with asthma. AIP has a higher value for predicting asthma than triglycerides and comparable value to high-density lipoprotein cholesterol.
Humans ; Child ; Retrospective Studies ; Blood Glucose ; Triglycerides ; Cholesterol, HDL ; Cholesterol, LDL ; Asthma/etiology* ; Dermatitis ; Risk Factors

Monascus is one of the most essential microbial resources in China, with thousands of years of history. Modern science has proved that Monascus can produce pigment, ergosterol, monacolin K, γ-aminobutyric acid, and other functionally active substances. Currently, Monascus is used to produce a variety of foods, health products, and pharmaceuticals, and its pigments are widely used as food additives. However, Monascus also makes a harmful polyketide component called citrinin in the fermentation process; citrinin has toxic effects on the kidneys such as teratogenicity, carcinogenicity, and mutagenicity (Gong et al., 2019). The presence of citrinin renders Monascus and its products potentially hazardous, which has led many countries to set limits and standards on citrinin content. For example, the citrinin limit is less than 0.04 mg/kg according to the Chinese document National Standard for Food Safety Food Additive Monascus (GB 1886.181-2016) (National Health and Family Planning Commission of the People's Republic of China, 2016), and the maximum level in food supplements based on rice fermented with Monascus purpureus is 100 µg/kg in the European Union (Commission of the European Union, 2019).
Citrinin ; Dietary Supplements ; Fungi ; Monascus

Child ; Humans ; Infant ; Esophagus ; Electric Power Supplies ; Eating ; Foreign Bodies

Objective: To analyze the clinical characteristics and complications of esophageal foreign bodies of button battery ingestion in children. Methods: A retrospective descriptive study included 83 children who were hospitalized in our hospital on account of button battery ingestion from January 2011 to December 2021. There were 50 males (60.2%) and 33 females (39.8%). The age ranged from 7.6 months to one month off 10 years, with a median age of 18 months. The data of patient demographics and time from ingestion to admission, location, symptoms, management, complications, and follow-up outcome were recorded. SPSS17.0 software was used for statistical analysis. Results: Seventy-two children (86.7%) were younger than 3 years old. The time from ingestion to admission ranged from 1 h to 2 months, with a median time of 8 h. Among the 63 children who were first diagnosed in our hospital, the most common clinical symptoms were nausea and vomiting (32 cases, 50.8%), dysphagia (31 cases, 49.2%), salivation (11 cases, 17.5%) and fever (10 cases, 15.9%). Seventy-three of 83 cases had complete preoperative diagnostic tests, and 55 cases (75.3%) were diagnosed by X-ray. In 56 cases (76.7%), the foreign badies were impacted in the upper third of esophagus. In 72 cases (86.7%), the foreign badies were removed by rigid esophagoscopy. 23 (27.7%) had serious complications, including tracheoesophageal fistula in 15 cases(TEF;65.2%), vocal cord paralysis (VCP;34.8%) in 8 cases, esophageal perforation in 3 cases (EP;13.0%), hemorrhage in 3 cases(13.0%), mediastinitis in 3 cases (13%), and periesophageal abscess in 1 case (4.3%). There were significant differences in the exposure time of foreign bodies and unwitnessed ingestion by guardians in the complications group (P<0.05). 2 cases died (2.4%)respectively due to arterial esophageal fistula bleeding and respiratory failure caused by stent displacement during the treatment of tracheoesophageal fistula. Conclusion: Accidental button battery ingestion can be life-threatening. and it mostly happens in children under 3 years old. Serious complications may happen cause of non-specific clinical manifestations and unwitnessed ingestions. Anterior and lateral chest X-ray is the first examination choice. Tracheoesophageal fistula is the most common serious complication.
Male ; Female ; Child ; Humans ; Infant ; Child, Preschool ; Tracheoesophageal Fistula/etiology* ; Retrospective Studies ; Foreign Bodies/diagnosis* ; Eating

Humans ; Waldenstrom Macroglobulinemia ; Prospective Studies