Unlocking epigenetics for precision treatment of Ewing’s sarcoma

Ewing’s sarcoma(EWS)is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults.Despite the efficacy of chemoradiotherapy in some cases,the cure rate for patients with metastatic and recurrent disease remains low.Therefore,there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment.Epigenetic regulation,a crucial factor in physiological processes,plays a significant role in controlling cell proliferation,maintaining gene integrity,and regulating transcription.Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS.A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development.This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS,integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

Clinical characteristics of renal anastomotic hemangioma

In this editorial,we comment on the article by Chen and Cai.We focus on renal anastomotic hemangioma,which is a rare benign hemangiomatous disease.This disease has unique clinical characteristics.Its biological behavior is benign,but its imaging results are similar to those of renal cancer.Renal anastomotic hemangioma is easy to misdiagnose and can lead to unnecessary radical nephrectomy.Therefore,urologists need a better understanding of this disease.We believe that patients with renal anastomotic hemangioma should receive individualized diagnosis and treatment to avoid overtreatment.

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Circ_0004592:An auxiliary diagnostic biomarker for gastric cancer

BACKGROUND Gastric cancer(GC)has a high mortality rate,and robust diagnostic biomarkers are currently lacking.However,the clinical relevance of circular RNAs(circRNAs)as GC biomarkers remains largely unexplored.AIM To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC.METHODS High-throughput sequencing of circRNAs was performed to screen for potential target molecules.Circ_0004592 expression was examined in GC tissues,cells,and plasma.Plasma samples were collected from healthy subjects’patients,as well as from patients with benign lesions,precancerous lesions,and GC,whereafter the diagnostic accuracy of circ_0004592 was evaluated.The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed.RESULTS Circ_0004592 was upregulated in both the tissue and plasma of patients with GC.Further,circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC.In the same patient,the postoperative plasma level of circ_0004592 was lower than that in the preoperative period.Moreover,circ_0004592 level was significantly correlated with tumor differentiation,tumor depth,and lymph node metastasis.The area under the curve(AUC)of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors.Diagnosis based on circ_0004592,carcinoembryonic antigen,and cancer antigen 199 achieved a superior AUC and was highly sensitive.CONCLUSION Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

Clinical characteristics and prognosis of takotsubo syndrome patients in single center

Takotsubo syndrome(TTS)is a clinical syndr-ome that frequently occurs in postmenopausal women,mostly induced by stress factors.It is characterized by chest pain,ST-segment elevation,and/or T-wave changes in electrocardiogram,along with my-ocardial troponin elevation.[1]TTS can be easily misdia-gnosed as myocardial infarction,and improper treatme-nt may lead to serious consequences.There are few re-ports and research on this disease.[2]

Treatment of Coronary Heart Disease from the Perspective of Liver Controlling Dispersion

The liver is in charge of distributing and regulating the movement of qi throughout the whole body,coordinating the transportation and transformation of the internal organs in the middle part of the body,promoting the biochemical circulation of qi,blood,and body fluids,and regulating emotions.Liver dysfunction can disrupt the transportation and transformation of qi,blood,and body fluids,causing phlegm turbidity,blood stasis,and other unwanted symptoms.Poor regulation of emotion further aggravates the accumulation of pathological substances,resulting in the obstruction of heart vessels,and ultimately coronary heart disease(CHD).Through regulating lipid metabolism,inflammatory reaction,vasoactive substances,platelet function,neuroendocrine,and other factors,liver controlling dispersing qi plays a comprehensive role in the prognosis of atherosclerosis,the primary cause of CHD.Therefore,it is recommended to treat CHD from the perspective of liver-controlling dispersion.

Analysis of the Mechanism of Intervention of Fangxiangxiaozhi Prescription on Dyslipidemia Based on Network Pharmacology and Molecular Docking

Objective: To explore the mechanism of intervention of Fangxiangxiaozhi prescription on dyslipidemia by using network pharmacology and molecular docking. Methods: The traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Pubchem, Uniprot, and other databases were adopted to screen the active ingredients and the corresponding targets of Fangxiangxiaozhi prescription. Dyslipidemia-related targets were identified using the databases of Disgenet and GeneCards. Then, the intersection target of drugs and diseases was demonstrated via a Venn diagram. Cytoscape3.7.2 was used to construct a “drugs-active ingredients-intersection targets” network map and the key active ingredients with the top 7-degree values were determined. The protein interaction network and topology analysis of the intersection target genes were carried out by combining STRING11.0 and Cytoscape3.7.2. Moreover, the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the intersection target genes were carried out using the Metascape database. Lastly, the key active ingredients and targets were molecular docked by AutoDockTools, Pymol, and other software. Results: There were 51 active components and 509 target genes of which 74 intersect with dyslipidemia. The key targets included tumor necrosis factor (TNF), interleukin-6 (IL-6), AKT1, PPAR gamma (PPARG), VEGFA, and PPARα. GO enrichment analysis obtained 1040 biological processes, 33 cell components, and 84 molecular functions;KEGG enrichment analysis obtained 148 pathways. The molecular docking results showed that the key targets and compounds exhibited good binding force. Conclusion: The active ingredients of Fangxiangxiaozhi prescription regulated several pathways through multiple targets to intervene in dyslipidemia. This study can serve as a foundation for further research.

Management of regional citrate anticoagulation for continuous renal replacement therapy:guideline recommendations from Chinese emergency medical doctor consensus

Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.

Investigation of the First Spermatorrhea Age of Males in Jiangsu Province, China

Background: The growth of adolescents is affected by economic development and education levels. We investigated the first spermatorrhea age of adolescents in urban area and in rural area of Jiangsu province, China. Methods: The data were obtained through anonymous questionnaire by using cross-sectional methods. From May 2016 to March 2017 in Jiangsu province, China, a total of 2131 Han nationality students were enrolled in cluster. The survey was contained date of birth, age, grade, age of first spermatorrhea and how long ago of the first spermatorrhea, all data were analyzed by Prism 8.0. Results: The questionnaire accounted for response was 97.3%, and the effective rate was 96.3%. The mean age of first spermatorrhea was (13.7 ± 1.5) years old, which included 13.6 ± 1.4 years in urban and 13.9 ± 1.5 years in rural. The first spermatorrhea occurred in the fifth and sixth grade primary school, and 1, 2, 3 grades of junior high school were 3.5%, 13%, 27.4%, 28.5% and 15.1%, respectively. There was 62.3% of first spermatorrhea occurred in summer. The rate of spermatorrhea with natural occurrence accounted for 95.1%, and with active accounted for 4.9%. Conclusions: Compared with rural area, the age of the first spermatorrhea of males in urban area is significant earlier. The adolescent’s first spermatozoa were mostly occurred in summer. The relevant physical and reproductive education should be started from the third grade of primary school. The reproductive health education should be carried out when the youth are 7 years old.

Construction of a prognostic signature of m7G-related lncRNAs in bladder cancer:a bioinformatics analysis

Background:N7-methylguanosine(m7G)-related plays an important role in the occurrence and development of tumors,and some recent studies have pointed out that long non-coding RNA is involved in the occurrence and development of various cancers.However,there is no literature on how m7G-related lncRNAs predict the prognosis of bladder cancer.The purpose of this study was to develop a predictive feature based on long non-coding RNA(lncRNAs)associated with m7G to predict the prognosis of patients with bladder cancer.Methods:We obtained the RNA transcriptome data and clinical data of bladder cancer patients through the cancer genome atlas database,and obtained the lncRNAs related to m7G by co-expression analysis and Cox regression analysis.Then the signature was evaluated by receiver operating characteristic curve and nomogram,and single sample gene set concentration analysis was used to study the correlation between the predictive model and tumor immune microenvironment in high-risk and low-risk groups.Results:We got a total of 5 m7G related lncRNA(MAFG-DT,AP003352.1,AC242842.1,AC024060.1,FAM111A-DT),which may be related to the prognosis of patients with bladder cancer.For predicting 1-,3-and 5-year survival rates,the area under the receiver operating characteristic curve was 0.757 and 0.722 and 0.739,respectively.Kaplan-Meier analysis showed that the prognosis of bladder cancer patients in high risk group was worse than that in low risk group.Immunoassay showed that the immune function of patients with bladder cancer in high risk group was more active.Conclusion:Prognostic markers based on m7G-related lncRNAs can be used to independently predict the prognosis of patients with bladder cancer and provide therapeutic targets for future clinical treatment.

拥抱未来:将ChatGPT融入中国护理教育

探讨ChatGPT在快速发展的人工智能领域中所扮演的角色,特别是其在护理教育领域内的巨大潜力。学术界对ChatGPT的关注日益增长,其在促进互动学习和提供实时反馈方面取得显著进展,ChatGPT在护理学科包括多个临床教学及场景中的应用研究成果,展现了其在多学科教育和解决临床问题方面的巨大潜力。通过比较多个大型语言模型在中国护理执业资格考试中的表现,发现ChatGPT相较于其他模型显示出更高的正确率,为其在中国护理教育和临床场景中的应用提供了坚实的理论基础。为了在本土化护理教育中有效利用ChatGPT,并承担起相应的责任,相关教育机构需要建立一个针对性的、有效的监管框架。通过规范化的使用者培训和对现有教育评估方法的调整,旨在防止潜在的误用和滥用,充分挖掘ChatGPT作为中国护理教育中的创新辅助工具的潜能,以适应现代化教学方法的发展需求。

Unusual early-stage pancreatic sarcomatoid carcinoma

Sarcomatoid carcinoma of the pancreas(SCP)is a very rare pathological type of carcinoma that usually has a poor prognosis.Its pathogenesis has not been elucidated.We herein report a case of an early-stage SCP involving successful treatment and a good prognosis.The patient was a 48-year-old Chinese man with a5-mo history of vague abdominal pain.Ultrasonography revealed a 93 mm×94 mm×75 mm mass of mixed echogenicity in the tail of the pancreas.Laboratory test results were within the normal range,with the exception of an obviously increased pretreatment neuron-specific enolase level.The plasma transforming growth factor(TGF)β1 and interleukin-11 levels were obviously increased according to enzyme-linked immunosorbent assay.Microscopically,the excised tumor tissue comprised cancer cells and mesenchymal cells.Immunohistochemical analysis was positive forα-1-antichymotrypsin,pan-cytokeratin,cytokeratin 19,cytokeratin 8/18,and vimentin and negative for CD68and lysozyme.The pathogenetic mechanism of this case shows that TGFβ1 may regulate the epithelial-tomesenchymal transition in SCP.With early eradication of the tumor and systemic therapy,this patient has been alive for more than 3 years without tumor recurrence or distant metastasis.This case is also the first to show that TGFβ1 may regulate the epithelial-tomesenchymal transition in early-stage SCP.

Management of isolated superior mesenteric artery dissection

AIM: To evaluate our experience of the clinical management of spontaneous isolated superior mesenteric artery dissection (ISMAD).

Expression and significance of mi R-654-5p and mi R-376b-3p in patients with colon cancer

BACKGROUND The relationship between micro RNAs,such as miR-654-5 p and miR-376 b-3 p,and the prognosis of colon cancer has not been studied until now.AIM To evaluate the expression levels of miR-654-5 p and miR-376 b-3 p and their clinical significance in colon cancer.METHODS RT-q PCR was performed to evaluate miR-654-5 p and miR-376 b-3 p expression in34 pairs of colon cancer and adjacent noncancerous tissues.Subsequently,the association of miR-654-5 p and miR-376 b-3 p expression with clinical factors or the survival of patients suffering from colon cancer was determined by using The Cancer Genome Atlas.RESULTS miR-654-5 p was upregulated and miR-376 b-3 p was downregulated in colon cancer tissues compared with adjacent noncancerous tissues(P<0.001).Increased miR-654-5 p and decreased miR-376 b-3 p expression levels weresignificantly associated with metastasis and clinical stage.Moreover,a univariate analysis demonstrated that colon cancer patients with high miR-654-5 p or low miR-376 b-3 p expression(P=0.044 and 0.007,respectively)had a poor overall survival rate.A multivariate analysis identified high miR-654-5 p expression and low miR-376 b-3 p expression as independent predictors of poor survival in colon cancer patients.CONCLUSION Upregulated miR-654-5 p and downregulated miR-376 b-3 p may be associated with tumour progression in colon cancer,and these micro RNAs may serve as independent prognostic markers for colon cancer.

A Nomogram Model for Predicting Type-2 Myocardial Infarction Induced by Acute Upper Gastrointestinal Bleeding

Objective To examine the independent risk factors of type-2 myocardial infarction(T2MI)elicited by acute upper gastrointestinal bleeding(AUGIB),and to establish a nomogram model for the prediction of AUGIB-induced T2MI.Methods A nomogram model was established on the basis of a retrospective study that involved 533 patients who suffered from AUGIB in the Department of Critical Care Medicine(CCM)or Emergency Intensive Care Unit(EICU)of Renmin Hospital of Wuhan University,Wuhan,China,from January 2017 to December 2020.The predictive accuracy and discriminative power of the nomogram were initially evaluated by internal validation,which involved drawing the receiver operating characteristic(ROC)curve,calculating the area under the curve(AUC),plotting the calibration curve derived from 1000 resampled bootstrap data sets,and computing the root mean square error(RMSE).The predictive ability of the nomogram was further validated through the prospective and multicenter study conducted by the investigators,which enrolled 240 AUGIB patients[including 88 cases from Renmin Hospital of Wuhan University,73 cases from Qilu Hospital of Shandong University(Qingdao),and 79 cases from Northern Jiangsu People’s Hospital)],who were admitted to the Department of CCM or EICU,from February 2021 to July 2021.Results Among the 533 patients in the training cohort,78(14.6%)patients were assigned to the T2MI group and 455(85.4%)patients were assigned to the non-T2MI group.The multivariate analysis revealed that age>65,hemorrhagic shock,cerebral stroke,heart failure,chronic kidney disease,increased blood urea nitrogen,decreased hematocrit,and elevated D-Dimer were independent risk factors for AUGIB-induced T2MI.All these factors were incorporated into the nomogram model.The AUC for the nomogram for predicting T2MI was 0.829(95%CI,0.783-0.875)in the internal validation cohort and 0.848(95%CI,0.794-0.902)in the external validation cohort.The calibration curve for the risk of T2MI exhibited good consistency between the prediction by the nomogram and the actual clinical observation in both the internal validation(RMSE=0.016)and external validation(RMSE=0.020).Conclusion The nomogram was proven to be a useful tool for the risk stratification of T2MI in AUGIB patients,and is helpful for the early identification of AUGIB patients who are prone to T2MI for early intervention,especially in emergency departments and intensive care units.

An enriched environment reduces hippocampal inflammatory response and improves cognitive function in a mouse model of stroke

An enriched environment is used as a behavio ral intervention therapy that applies sensory,motor,and social stimulation,and has been used in basic and clinical research of va rious neurological diseases.In this study,we established mouse models of photothrombotic stroke and,24 hours later,raised them in a standard,enriched,or isolated environment for 4 weeks.Compared with the mice raised in a standard environment,the cognitive function of mice raised in an enriched environment was better and the pathological damage in the hippocampal CA1 region was remarkably alleviated.Furthermore,protein expression levels of tumor necrosis factor receptor-associated factor 6,nuclear factorκB p65,interleukin-6,and tumor necrosis factorα,and the mRNA expression level of tumor necrosis factor receptor-associated factor 6 were greatly lower,while the expression level of miR-146a-5p was higher.Compared with the mice raised in a standard environment,changes in these indices in mice raised in an isolated environment were opposite to mice raised in an enriched environment.These findings suggest that different living environments affect the hippocampal inflammatory response and cognitive function in a mouse model of stro ke.An enriched environment can improve cognitive function following stroke through up-regulation of miR-146a-5p expression and a reduction in the inflammatory response.

Onodera's Prognostic Nutritional Index is a novel and useful prognostic marker for gastrointestinal stromal tumors

BACKGROUND Immunoinflammatory markers such as the peripheral blood neutrophil-tolymphocyte ratio(NLR)and the platelet-to-lymphocyte ratio(PLR)have gained considerable attention as prognostic markers in gastrointestinal stromal tumors(GISTs).AIM To assess the prognostic value of Onodera’s Prognostic Nutritional Index(OPNI)for GISTs.METHODS All patients who had undergone surgical resection for a primary,localized GIST from 2009 to 2016 at our cancer center were initially and retrospectively identified.Recurrence-free survival(RFS)was calculated by the Kaplan-Meier method and compared by the log-rank test.We used multivariate Cox proportional hazard regression models to identify associations with outcome variables.RESULTS A total of 235 GISTs were identified and included for analysis under our inclusion criteria.Univariate and multivariate analyses both identified the OPNI as an independent prognostic marker,and the OPNI was associated with the primary site,tumor size,mitotic index,tumor rupture,necrosis,and modified NIH risk classification.Low OPNI(<51.30;hazard ratio=5.852;95% confidence interval:1.072–31.964;P=0.0414)was associated with worse RFS.The 2-and 5-year RFS rates of the patients with a low OPNI were 92.83% and 76.22%,respectively,whereas 100% and 98.41% were achieved by the patients with a high OPNI.CONCLUSION The preoperative OPNI is a novel and useful prognostic marker for GISTs.

Experience in the diagnosis and treatment of mesenteric lymphangioma in adults:A case report and review of literature

BACKGROUND Mesenteric lymphangioma(ML) in adults is a very rare disease. We report six hospitalized adult patients with ML in our hospital between January 2013 and July 2018 to investigate the characteristics and prognosis of ML in adults.CASE SUMMARY The male-to-female ratio was 3:3, and the median age at diagnosis was 55.2 years. Clinical manifestations varied; however, most were acute cases(5/6). No history of trauma was reported. None(0/6) of the patients were accurately diagnosed with ML in the emergency and outpatient departments. Mesenteric cysts were identified in four patients(66.7%) by abdominal ultrasound and in five patients(83.3%) by computed tomography. ML was postoperatively confirmed by pathology. Most MLs(4/6) were associated with infection of other systems. ML was located in the mesentery of the small intestine(n = 4), ileum(n = 1) and rectum(n = 1). Cyst fluid was clear(n = 4), chylous(n = 1) and bloody(n = 1). Surgical procedures included complete tumor removal and partial intestinal excision(n = 6). Recurrence and adhesive intestinal obstruction were not observed during the 3-12 mo follow-up period.CONCLUSION ML in adults is a rare benign acquired disease that can be cured by surgical treatment. Infection may be a cause of ML.

Diaphragmatic suture with tubular stomach to prevent early delayed gastric emptying after esophagectomy

Objective The objective of this study was to evaluate the clinical efficacy of a diaphragmatic suture with tubular stomach to prevent delayed gastric emptying(DGE) after esophagectomy through the cervico-thoracoabdominal approach. Methods A total of 980 patients with esophageal cancer undergoing esophagectomy through the cervico-thoracoabdominal approach were retrospectively included in this study and divided into two groups. All patients underwent tubular stomach creation(group A; n = 530) or a diaphragmatic suture and tubular stomach creation(group B; n = 450). The incidence of early DGE was observed. Results The incidence of early DGE in group A was significantly higher than that in group B(P < 0.05). Conclusion This observation study suggests that the use of a diaphragmatic suture with tubular stomach through the cervico-thoracoabdominal approach can decrease the incidence of early DGE after esophagectomy.

Rigid ureteroscopy in prone split-leg position for fragmentation of female ureteral stones:A case report

BACKGROUND Ureteroscopy is widely used in the treatment of ureteral stones due to the increased morbidity of turolithiasis.This is the first report of a case of ureteral calculi treated with rigid ureteroscopy in the modified prone split-leg position.CASE SUMMARY A 62-year-old Asian woman was diagnosed with a ureteral stone and underwent extracorporeal shock wave lithotripsy twice.However,the abdominal computer tomography scan showed persistent calculi on the right lower ureter.Her left hip movement was limited because of a left femoral neck fracture that did not receive proper treatment in a timely manner.She was unable to undergo surgery in the lithotomy position and refused to accept flexible ureteroscopy treatment.Therefore,rigid ureteroscopy was performed with her in the modified prone split-leg position.The ureteral calculi were successfully fragmented.CONCLUSION It is feasible to treat lower ureteral calculi in women in the prone split-leg position with the implementation of rigid ureteroscopy.