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.

The scientific evaluation of the construction and development of university disciplines is an important part and a key challenge in China’s “Double First-Class” initiative. Based on the ESI and InCites databases, this study conducted a year-long observation and analysis of the disciplines at universities in Jiangsu Province under the “Double First-Class” framework. The research focused on the development trends of potential and emerging disciplines, while exploring the influence of traditional predominant disciplines on the growth of these emerging fields and the pathways through which such influence might occur. The study aims to provide some reference and insights for the development of disciplines in the universities in Jiangsu. The findings reveal that, overall, the discipline development maturity of the universities is high, with a positive growth trend and significant development potential in certain fields, which are strongly supported by the traditional predominant disciplines. However, an imbalance in the development across various discipline categories has also been observed. Looking ahead, universities are encouraged to capitalize on their unique academic strengths to foster collaborative development, emphasize the growth of social science disciplines, promote interdisciplinary integration, and cultivate high-level talent for society. This approach will better facilitate the establishment of high-level universities and contribute to the realization of the goal of building a strong educational nation.

Objective To investigate the trends in the global burden due to cystic echinococcosis from 1990 to 2021, and to predict the global burden of cystic echinococcosis from 2022 to 2035, so as to provide insights into formulation of the cystic echinococcosis control strategy. Methods The global age-standardized prevalence, mortality, disability-adjusted life years (DALYs) rates and their 95% uncertainty intervals (UI) of cystic echinococcosis from 1990 to 2021 were captured from the Global Burden of Disease Study 2021 (GBD 2021) database, and the trends in the global burden of cystic echinococcosis from 1990 to 2021 were analyzed using the Joinpoint regression model. The associations between the global burden of cystic echinococcosis and socio-demographic index (SDI) were examined using a smoothing spline model and frontier analysis, and the global burden of cystic echinococcosis was projected from 2022 to 2035 using the Bayesian age-period-cohort (BAPC) model. Results The global agestandardized prevalence, mortality and DALYs rates of cystic echinococcosis were 7.69/10⁵ [95% UI: (6.27/10⁵, 9.51/10⁵)], 0.02/10⁵ [95% UI: (0.01/10⁵, 0.02/10⁵)], and 1.32/10⁵ [95% UI: (0.99/10⁵, 1.69/10⁵)] in 2021. The global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a rise by 0.14% per year from 1990 to 2021, and the global age-standardized mortality and DALYs rates of cystic echinococcosis appeared a tendency towards a decline by 4.68% and 4.01% per year from 1990 to 2021, respectively. Joinpoint regression analysis showed that global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a decline from 1990 to 2000 [annual percent change (APC) = −0.66%, 95% confidence interval (CI): (−0.70%, −0.61%)] and from 2005 to 2015 [APC = −0.88%, 95% CI: (−0.93%, −0.82%)], and towards a rise from 2000 to 2005 [APC = 3.68%, 95% CI: (3.49%, 3.87%)] and from 2015 to 2021 [APC=0.30%, 95%CI: (0.19%, 0.40%)].Theagestandardized prevalence (r = −0.17, P < 0.05), mortality (r = −0.67, P < 0.05) and DALYs rates of cystic echinococcosis (r = −0.60, P < 0.05) all correlated negatively with SDI across 21 geographical regions from 1990 to 2021, and the age-standardized mortality (r = −0.61, P < 0.05) and DALYs rates (r = −0.44, P < 0.05) both correlated negatively with SDI across 204 countries and territories in 2021. Frontier analysis revealed that the age-standardized DALYs rate of cystic echinococcosis was still not in line with the frontier in some high-SDI countries or territories. In addition, the global age-standardized prevalence was projected with the BAPC model to appear a tendency towards a rise among both men [estimated annual percent change (EAPC) = 0.18%, 95% CI: (0.13%, 0.23%)] and women [EAPC = 0.29%, 95% CI: (0.24%, 0.34%)] from 2022 to 2035, and the global age-standardized mortality [men: EAPC = −4.71%, 95% CI: (−4.71%, −4.37%); women: EAPC = −4.74%, 95% CI: (−4.74%, −4.74%)] and DALYs rates [men: EAPC = −3.35%, 95% CI: (−3.36%, −3.34%); women: EAPC = −3.17%, 95% CI: (−3.18%, −3.16%)] were projected to appear a tendency towards a decline among both men and women. Conclusions The global burden of cystic echinococcosis appeared an overall tendency towards a decline from 1990 to 2021; however, the global prevalence of cystic echinococcosis is projected to appear a tendency towards a rise from 2022 to 2035. Intensified cystic echinococcosis control programmes are recommended.

OBJECTIVE To systematically investigate the changes of volatile components in Euphorbia wallichii after milk and wine processing， and preliminarily elucidate the material basis for reducing toxicity. METHODS Using headspace gas chromatography-mass spectrometry technology， the volatile components in raw E. wallichii， milk-processed E. wallichii， and wine- processed E. wallichii were isolated and identified， and the relative percentage content of each component was calculated by the peak area normalization method. Combining chemometric methods such as principal component analysis and orthogonal partial least- squares discriminant analysis， changes in volatile components in samples after milk and wine processing were compared. Differential components were screened. RESULTS A total of 66 volatile components were identified from the three samples， with the types of compounds primarily comprising alkanes， olefins， heterocycles and esters， among others. A total of 39， 24 and 36 volatile components were identified from raw E. wallichii， milk-processed E. wallichii， and wine-processed E. wallichii， respectively， with 10 components common to all three preparations. Compared with raw E. wallichii， the relative percentage of other components in milk-processed E. wallichii decreased， except for alkanes and esters. The relative percentage of alkanes， olefins， aldehydes and esters in wine-processed E. wallichii increased， but the contents of heterocyclic compounds， ketones， ethers and alcohols decreased. The results of chemometric analysis showed that the volatile components of raw and processed products were significantly different. A total of 5 kinds of differential components in milk-processed products and 3 kinds of differential components in wine-processed products were screened out. Among them， the relative percentage of potential toxic components such as linalool， octanal and 3-pentanone decreased significantly after processing（P＜0.05）. CONCLUSIONS Milk and wine processing may exert a toxicity-reducing effect by reducing the contents of toxic components such as linalool， octanal and 3-pentanonein E. wallichii.

Among the current curricula of medical teaching in China, most courses focus on the integrated teaching of a single organ-system combination, while there are relatively a few integrated courses that focus on the multiple dimensions between different organs and systems and between medical sciences and social sciences. In 2016, Chongqing Medical University started to cooperate with University of Leicester to establish the clinical medicine major and introduced the course of Integration for Clinical Application (ICA) that had been run well in University of Leicester for years. With reference to the education goal of our university, the curriculum group adopted a series of actions for the localization of this course from the aspects of teaching objectives, contents, teaching model, education resources, and quality of faculty. After the completion of the first round of this course, the passing rate reached 86.96%(100/115) in the quantified evaluation of accomplishment, which was higher than the passing rate of other courses introduced from University of Leicester. The quantitative expert assessment of this course also ranked among the top courses in our university, and student assessment showed that the ability indicators were improved by 25.00%- 38.00%. The above data show that good results have been achieved for the curriculum localization of ICA.

Objective To analyze the factors affecting the prognosis of patients with knee osteoarthritis,and to construct a nomogram prediction model in conjunction with multi-dimensional clinical indicators.Methods The clinical data of 234 pa-tients with knee osteoarthritis who were treated in our hospital from January 2015 to June 2021 were retrospectively analyzed,including 126 males and 108 females;age more than 60 years old for 135 cases,age less than 60 years old for 99 cases.Lysholm knee function score was used to evaluate the prognosis of the patients,and the patients were divided into good progno-sis group for 155 patients and poor prognosis group for 79 patients according to the prognosis.The clinical data of the subjects in the experimental cohort were analyzed by single factor and multiple factors.The patients were divided into experimental co-hort and verification cohort,the results of the multiple factor analysis were visualized to obtain a nomogram prediction model,the receiver operating characteristic curve(ROC),calibration curve and decision curve were used to evaluate the model's dis-crimination,accuracy and clinical benefit rate.Results The results of multivariate analysis showed that smoking,pre-treatment K-L grades of Ⅲto Ⅳ,and high levels of interleukin 6(IL-6)and matrix metallo proteinase-3(MMP-3)were risk factors for the prognosis of patients with knee osteoarthritis.ROC test results showed that the area under the curve of the nomogram model in the experimental cohort and validation cohort was 0.806[95％CI(0.742,0.866)]and 0.786[(95％CI(0.678,0.893)],re-spectively.The results of the calibration curve showed that the Brier values of the experimental cohort and verification cohort were 0.151 points and 0.134 points,respectively.When the threshold probability value in the decision curve was set to 31％,the clinical benefit rates of the experimental cohort and validation cohort were 51％and 56％,respectively.Conclusion The prognostic model of patients with knee osteoarthritis constructed based on multi-dimensional clinical data has both theoretical and practical significance,and can provide a reference for taking targeted measures to improve the prognosis of patients.

Objective To investigate the predictive value of cardiac magnetic resonance(CMR)late gadolinium enhancement(LGE)on the long-term risk of sudden cardiac death(SCD)in hypertrophic cardiomyopathy(HCM).Methods A total of 81 patients with HCM who received CMR-LGE in our hospital from October 2013 to June 2020 were selected as the study subjects,the basic data,5-year HCM-SCD risk score and LGE values of all patients,and the incidence of SCD were counted.Pearson correlation analysis was used to analyze the correlation of LGE values and 5-year HCM-SCD risk score in patients with HCM,and ROC curves was drawn to calculate the predictive efficacy of LGE values on the occurrence of SCD in patients with HCM.Results The LGE values of patients with HCM increased significantly with the 5-year HCM-SCD risk score increasing(P<0.01);Pearson correlation analysis showed that the LGE values of patients with HCM was positively correlated with 5-year HCM-SCD risk score(r=0.704,P<0.01);The ROC curve analysis revealed that the AUC of LGE values of patients with HCM predicting the risk of SCD in patients with HCM was 0.892,meanwhile,the LGE≥5.47 was the optimal threshold,with diagnostic sensitivity of 100%,and the specificity of 66.67%;The results of the Kaplan-Meier survival analysis showed that the survival rate of the LEG≥5.47 group was significantly lower than that of the LGE<5.47 group(P<0.01).Conclusion The LGE value of patients with HCM can effectively predict the risk of SCD.When the LGE value of HCM patients is≥5.47%,implantable cardioverter defibrillator should be considered for primary prevention in advance to improve the risk stratification of SCD in HCM patients.

Objective To verify the safety and efficacy of a new portable extracorporeal membrane oxygenation(ECMO)system(Xijing Advanced Life Support System JC-Ⅲ)in large animals.Methods A total of 10 healthy small fat-tail sheep underwent veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support by carotid arterial-jugular catheterization to evaluate the performance of the JC-Ⅲ ECMO system.Systemic anticoagulation was achieved by continuous infusion of heparin.Active coagulation time(ACT)was recorded every 2 hours during the experiment,and the ACT was maintained between 200-250 s.Centrifugal pump speed is set at 3 000-3 500 r/min.The changes of hemoglobin,blood cell counts,hematocrit,liver and kidney function were monitored before and 24 h after ECMO initiation,respectively.After the experiment,the pump and oxygenator were dissected to probe the thrombosis.Results The success rate of VA-ECMO operation was 100％,and there was no hemolysis,pump thrombosis and oxygenator thrombosis after 24 h of ECMO.Before and after the operation,there were no significant changes in indicators such as hemoglobin content,white blood cell counts,platelet counts,alanine aminotransferase concentration,aspartate aminotransferase concentration,urea,creatinine,high-sensitivity troponin Ⅰ,and N-terminal pro-brain natriuretic peptide(all P＞0.05).Conclusions This in vivo study confirms that Xijing Advanced Life support System JC-Ⅲ is safe and effective.

Objective:To investigate the impacts of fatty acid binding protein 4(FABP4)silencing on endoplasmic reticulum stress(ERS)and insulin resistance(IR)in gestational diabetes mellitus(GDM)rats by regulating protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)/transcription factor 4(ATF4)/C/EBP homologous protein(CHOP)signaling pathway.Methods:GDM rat model was established by intraperitoneal injection of streptozotocin(STZ).Rats were injected with FABP4 siRNA plasmid(si-FABP4),negative control plasmid(NC)and PERK activator(CCT020312)via tail vein,and were randomly grouped into Normal group,GDM group,GDM+NC group,GDM+si-FABP4 group and GDM+si-FABP4+CCT020312 group.The levels of FABP4,blood lipids,inflammatory markers and oxidative stress markers in pancreatic tissue were detected,the expres-sions of PERK/eIF2α/ATF4/CHOP signaling pathway-related proteins in pancreatic tissue were detected.HTR-8/SVneo cells were divided into 5 groups:Control group,high glucose(HG)group,HG+NC group,HG+si-FABP4 group,HG+si-FABP4+CCT020312 group.After 24 h,the expressions of FABP4 and PERK/eIF2α/ATF4/CHOP signaling pathway related proteins were detected.Results:Compared with Normal group,the level of FABP4 in the serum and pancreatic tissue of the GDM group were obviously up-regu-lated(P<0.05).FABP4 silencing obviously reduced FBG and IR,decreased the levels of blood lipids,CRP,TNF-α,IL-6 and MDA,and increased the levels of SOD and CAT(P<0.05).Furthermore,FABP4 silencing attenuated pancreatic and placental tissue damages.After CCT020312 up-regulated the phosphorylation levels of PERK and eIF2α and the protein expressions of ATF4 and CHOP,the inhibitory effects of FABP4 silencing on IR,inflammation,oxidative stress,and pancreatic and placental damages in GDM rats were reversed(P<0.05).FABP4 was up-regulated in HTR-8/SVneo cells induced by HG,and silencing FABP4 inhibited the protein ex-pression of the PERK/eIF2α/ATF4/CHOP pathway,while CCT020312 reversed this change(P<0.05).Conclusion:FABP4 silencing improves IR and ERS in GDM rats by inhibiting inflammation and oxidative stress,and the mechanism is related to the inhibition of PERK/eIF2α/ATF4/CHOP signaling pathway.

Objective Establishment and evaluation of a mouse model of aldosterone-induced multi-organ damage.Methods Twenty mice were randomly divided into four groups,with five mice in each group:a blank control group(0 μg/(kg·d)),a low-dose aldosterone group(150 μg/(kg·d))),a medium-dose aldosterone group(300 μg/(kg d)),and a high-dose aldosterone group(450 pug/(kg·d)).Aldosterone-containing osmotic minipumps were surgically implanted under the skin,and aldosterone was infused for 4 weeks to establish the aldosterone-induced damage model.The body weight and blood pressure of the mice were recorded weekly.After the 4 week modeling period,the mice were euthanized,and their tissues were collected for observation and analysis of blood pressure and histological morphology of various organs.Results(1)After 4 weeks of aldosterone infusion,the serum aldosterone levels were significantly increased in the medium-dose and high-dose aldosterone groups,but not in the low-dose aldosterone group.(2)After the implantation of osmotic minipumps,the systolic blood pressure was significantly increased in the low-dose,medium-dose,and high-dose aldosterone groups during the second and third weeks,but decreased in all these groups during the fourth week.(3)The kidney and heart in the low-dose,medium-dose,and high-dose aldosterone groups showed varying degrees of damage,interstitial edema,collagen deposition,and fibrotic lesions.The liver in the low-dose aldosterone group showed a small amount of collagen deposition,while the medium-dose and high-dose aldosterone groups showed varying degrees of hepatocyte damage,collagen deposition,and fibrotic lesions.Conclusions Aldosterone can induce multi-organ damage in mice.Under this modeling method,organ damage is mainly manifested as edema,collagen deposition,and fibrotic lesions.