Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis

BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

Dynamic interaction nursing intervention on functional rehabilitation and self-care ability of patients after aneurysm surgery

BACKGROUND Nursing practices based on the dynamic interaction model have been shown to be superior to generic nursing practices.However,whether this model is effective in patients recovering from intracranial aneurysm surgery is not well studied.AIM To investigate the effect of nursing based on a dynamic interaction model on functional rehabilitation of patients after aneurysm surgery.METHODS A total of 86 cases in our hospital with intracranial aneurysm from April 2019 to April 2021,were selected and divided into the study group and the control group,with 43 patients in each group.The control group received routine nursing,and the research group received nursing intervention based on a dynamic interaction model.The daily living ability(activities of daily living,ADL),cognitive function(Simple Intelligent Mental State Scale,MMSE),quality of life(Generic Quality of Life Inventory-74,GQOL-74),self-care ability(Exercise of Self-Care Agency scale),incidence of complications,and nursing satisfaction were recorded before and after intervention.RESULTS Before intervention,ADL(52.09±6.44),MMSE(18.03±4.11),and GQOL-74(53.68±4.34)scores in the study group were not significantly different from those in the control group(ADL:50.97±7.32,MMSE:17.59±3.82,GQOL-74:55.06±3.98)(P>0.05).After intervention,ADL(86.12±5.07),MMSE(26.64±2.66),and GQOL-74(83.13±5.67)scores in the study group were higher than those in the control group(ADL:79.81±6.35,MMSE:24.51±3.00,and GQOL-74:77.96±6.27)(P<0.05).Before intervention,self-concept(17.46±4.44),self-care skills(25.22±4.20),self-care knowledge(22.35±4.74),and self-care responsibility(15.06±3.29)scores in the study group was similar to those in the control group(self-concept:16.89±5.53,self-care skills:24.59±4.46,self-care knowledge:21.80±3.61,and self-care responsibility:14.83±3.11)(P>0.05).After the intervention,self-concept(26.01±3.18),self-care skills(37.68±6.05),self-care knowledge(45.56±5.83),and self-care responsibility(22.01±3.77)scores in the study group were higher than those in the control group(self-concept:22.97±3.46,self-care skills:33.02±5.65,selfcare skills knowledge:36.81±5.54,and self-care responsibility:17.97±3.56 points)(P<0.05).The incidence of complications in the study group(4.65%)was lower than that in the control group(18.60%)(P<0.05).Nursing satisfaction in the study group(95.35%)was higher than that in the control group(81.40%)(P<0.05).CONCLUSION Nursing intervention based on a dynamic interaction model can improve postoperative cognitive function,daily living ability,self-care ability,quality of life,and patient satisfaction,while reducing the risk of complications.

Abnormal resting-state functional network centrality in patients with high myopia： evidence from a voxel-wise degree centrality analysis

AIM： To investigate the functional networks underlying the brain-activity changes of patients with high myopia using the voxel-wise degree centrality（DC） method.METHODS： In total, 38 patients with high myopia（HM）（17 males and 21 females）, whose binocular refractive diopter were-6.00 to-7.00 D, and 38 healthy controls（17 males and 21 females）, closely matched in age, sex, and education levels, participated in the study. Spontaneous brain activities were evaluated using the voxel-wise DC method. The receiver operating characteristic curve was measured to distinguish patients with HM from healthy controls. Correlation analysis was used to explore the relationship between the observed mean DC values of the different brain areas and the behavioral performance.RESULTS： Compared with healthy controls, HM patients had significantly decreased DC values in the right inferior frontal gyrus/insula, right middle frontal gyrus, and right supramarginal/inferior parietal lobule（P〈0.05）. In contrast, HM patients had significantly increased DC values in the right cerebellum posterior lobe, left precentral gyrus/postcentral gyrus, and right middle cingulate gyrus（P〈0.05）. However, no relationship was found between the observed mean DC values of the different brain areas and the behavioral performance（P〉0.05）.CONCLUSION： HM is associated with abnormalities in many brain regions, which may indicate the neural mechanisms of HM. The altered DC values may be used as a useful biomarker for the brain activity changes in HM patients.

基于BI-RADS分类多参数乳腺MRI对肿块性病变的诊断效能研究

目的评价乳腺MRI乳腺影像报告和数据系统(BI-RADS)分类各观察指标对肿块性乳腺病变的阳性预测价值(PPV)及诊断效能;探讨乳腺肿块性病变的动态增强磁共振(DCE-MRI)征象、功能磁共振成像(DWI-ADC)值联合应用对该类良、恶性病变诊断的价值。方法回顾性分析194例乳腺肿块性病变,计算BI-RADS分类各指标的PPV,并分析MRI常规检查(形态、边界、边缘及内部强化方式)、动态增强扫描[时间-信号曲线(TIC)]和DWI结果:以病理结果为"金标准",分别得出PPV和Kappa值。结果194例肿块性病变中,BI-RADS 3~5类PPV分别为0.114、0.286、0.904;依据MRI BI-RADS词汇形态学描述,形态不规则PPV为0.780,边缘不规则/毛刺PPV为0.849,边缘强化PPV为0.889;TIC平台型和流出型PPV分别为0.613和0.833;ADC值≤1.18×10^(-3) mm^2/s PPV高达0.901。形状、病灶强化方式与病理结果吻合度较弱kappa值分别为0.410和0.386,边界与病理结果吻合度检验水平一般kappa值0.570。TIC曲线及ADC值与病理结果吻合度检验水平较高kappa值分别为0.735和0.823。Logistic回归分析结果表明ADC值、边缘及TIC类型对乳腺良、恶性病变的诊断能力较准确(OR=01.041,3.156和2.217),ADC值≤1.18×10^(-3) mm^2/s、边缘毛刺征、TICⅡ型和Ⅲ型为MRI诊断恶性乳腺肿块性病变的危险因素(OR=01.041,3.156和2.217)。结论运用BI-RADS词汇中的标准术语对乳腺MRI中肿块性病变特点进行严谨评估,对预测肿块性病变的恶性可能性有很大作用。边缘、TIC曲线及ADC值在乳腺良、恶性病变诊断中具有良好的诊断效能。

圆锥角膜发病的力学因素及其机制

圆锥角膜是一种以角膜进行性变薄前突为特征的角膜扩张性疾病。其发病机制尚不清楚。体外实验表明力学刺激可能通过升高氧化应激水平和炎症因子浓度而损伤角膜基质细胞,造成角膜细胞外基质降解等一系列变化。大量临床研究证实揉眼、由睡姿引起的眼球压迫等力学因素可能在圆锥角膜发生发展的过程中起重要作用。它们可能通过增加泪液炎症因子水平、造成眼压变化、改变角膜生物力学性能以及机械摩擦直接损伤角膜组织、升高角膜上皮温度等机制对角膜造成影响。本文就力学因素对角膜基质细胞、角膜组织的影响及其在圆锥角膜发病机制中可能的作用进行阐述,以期为预防和管理圆锥角膜提供参考。

Enriched environment enhances histone acetylation of NMDA receptor in the hippocampus and improves cognitive dysfunction in aged mice

The mechanisms of age-associated memory impairment may be associated with glutamate receptor function and chromatin modification.To observe the effect of an enriched environment on the cognitive function of mice with age-associated memory impairment,3-monthold C57BL/6 male mice("young"mice)were raised in a standard environment,while 24-month-old C57BL/6 male mice with memory impairment("age-associated memory impairment"mice)were raised in either a standard environment or an enriched environment.The enriched environment included a variety of stimuli involving movement and sensation.A water maze test was then used to measure cognitive function in the mice.Furthermore,quantitative real-time polymerase chain reaction and western blot assays were used to detect right hippocampal GluN2B mRNA as well as protein expression of GluN2B and CREB binding protein in all mice.In addition,chromatin immunoprecipitation was used to measure the extent of histone acetylation of the hippocampal GluN2B gene promoters.Compared with the young mice,the water maze performance of age-associated memory impairment mice in the standard environment was significantly decreased.In addition,there were significantly lower levels of total histone acetylation and expression of CREB binding protein in the hippocampus of age-associated memory impairment mice in the standard environment compared with the young mice.There were also significantly lower levels of histone acetylation,protein expression,and mRNA expression of GluN2B in the hippocampus of these mice.In contrast,in the age-associated memory impairment mice with the enriched environment intervention,the water maze performance and molecular biological indexes were significantly improved.These data confirm that an enriched environment can improve cognitive dysfunction in age-associated memory impairment mice,and suggest that the mechanisms may be related to the increased expression of CREB binding protein and the increased degree of total histone acetylation in the hippocampus of age-associated memory impairment mice,which may cause the increase of histone acetylation of GluN2B gene promoter and the enhancement of GluN2B mRNA transcription and protein expression in hippocampus.The animal experiment was approved by the Animal Ethics Committee of Yangzhou University,China(approval No.20170312001)in March 2017.

ESE1 expression correlates with neuronal apoptosis in the hippocampus after cerebral ischemia/reperfusion injury

Epithelial-specific ETS-1(ESE1), a member of the ETS transcription factor family, is widely expressed in multiple tissues and performs various functions in inflammation. During neuroinflammation, ESE1 promotes neuronal apoptosis; however, the expression and biological functions of ESE1 remain unclear after cerebral ischemia/reperfusion. We performed in vivo and in vitro experiments to explore the role of ESE1 in cerebral ischemic injury. A modified four vessel occlusion method was used in adult Sprague-Dawley rats. At 6, 12, 24, 48, and 72 hours after model induction, the hippocampus was collected for analysis. Western blot assays and immunohistochemistry showed that the expression of ESE1, phosphorylated p65 and active caspase-3 was significantly up-regulated after ischemia. Double immunofluorescence staining indicated that ESE1 and NeuN were mostly co-located in the hippocampus after ischemia. Furthermore, ESE1 was also co-expressed with active caspase-3. PC12 cells were stimulated with cobalt chloride(CoCl_2) to establish a chemical hypoxia model. After ESE1 knockdown by siRNA for 6 hours, cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. The levels of ESE1, phosphorylated p65 and active caspase-3 were also remarkably increased in PC12 cells after CoCl_2 stimulation. After ESE1 knockdown, PC12 cell viability was increased after hypoxia. siRNA knockdown of ESE1 decreased the level of p-p65 and active caspase-3 after CoCl_2 stimulation. These data reveal that ESE1 levels are elevated in the hippocampus after cerebral ischemia/reperfusion injury. This may play a role in neuronal apoptosis via activation of the nuclear factor-κB pathway.

二苯乙烯苷对HepG2细胞胆固醇含量的影响及其作用机制研究

目的探索二苯乙烯苷对HepG2细胞胆固醇含量的影响及其作用机制。方法将细胞随机分为正常组、模型组(ox-LDL 50 mg/L)、A组(ox-LDL 50 mg/L+二苯乙烯苷250μmol/L)、B组(ox-LDL50 mg/L+二苯乙烯苷188μmol/L)、C组(ox-LDL 50 mg/L+二苯乙烯苷125μmol/L)及D组(ox-LDL50 mg/L+二苯乙烯苷62.5μmol/L)。细胞处理48 h后,采用油红O脂肪染色法观察、胆固醇测定试剂盒测定各组胆固醇的含量并用逆转录聚合酶链反应检测肝癌HepG2细胞ABCG1、ABCA1及SR-BI的表达水平。结果正常组、A、B、C和D组细胞内总胆固醇(TC)、细胞内游离胆固醇(FC)含量均低于模型组(P <0.05),同时A、B、C和D组上清TC和FC含量较正常组升高(P<0.05)。二苯乙烯苷能够降低HepG2细胞内胆固醇含量,增加胆固醇外流率(P<0.05),其中二苯乙烯苷浓度为125μmol/L时达最高值。模型组细胞ABCA1 mRNA表达水平较正常组下降(P<0.05)。A、B、C和D组ABCA1、ABCG1和SR-BI mRNA表达水平较模型组上升(P<0.05)。结论二苯乙烯苷能够降低HepG2细胞胆固醇的含量,其机制可能是通过上调ABCA1、ABCG1和SR-BI的表达水平而增加胆固醇外流。

Multisystem involvement Langerhans cell histiocytosis in an adult:A case report

BACKGROUND Langerhans cell histiocytosis(LCH)is a rare condition wherein Langerhans cells proliferate abnormally,adversely impacting organs including lymph nodes,bones,skin,lungs,and pituitary gland.The LCH disease course varies widely among patients from a self-limiting condition to one that progresses rapidly and culminates in death.It is uncommon for multisystem LCH to be observed in adults.Herein we describe a woman suffering from multi-system LCH involvement.CASE SUMMARY A 37-year old Chinese woman was admitted to the hospital in June 2019 suffering from dyspnea that had progressed over the course of 5 years.Her medical history included:central diabetes insipidus(DI)that had been treated via radiotherapy,desmopressin acetate,and bromocriptine;bilateral pneumothorax with two surgeries having been performed to remove bullae;and autoimmune hepatitis that had been unsuccessfully treated using a combination of methylprednisolone and mycophenolate mofetil.A chest computed tomography(CT)scan revealed the presence of multiple pulmonary cysts of varying sizes.We re-analyzed right pulmonary bullae samples that had been removed in 2014,performed a systematic 18 F-FDG PET/CT analysis,and convened a multidisciplinary medical team to diagnose and treat this patient.As a result,we were able to eventually diagnose this patient with LCH that was not associated with BRAF-V600 E mutations.CONCLUSION We hope to emphasize the importance of systemic evaluation and of cooperation between multidisciplinary physicians with the goal of improving awareness and detection of this orphan disease.

Invasive aspergillosis presenting as hilar masses with stenosis of bronchus: A case report

BACKGROUND Hilar masses with stenosis of the bronchus occur mainly due to malignant diseases,such as lung cancer.Hilar masses resulting from invasive aspergillosis are extremely rare and occur mostly in severely immunosuppressed patients.CASE SUMMARY In the current case report,we have documented a unique case of invasive aspergillosis presenting as a mass in the hilum and bronchial stenosis under bronchoscopy mimicking lung cancer in a 54-year-old man with diabetes mellitus.The histological analysis of bronchial membrane biopsy demonstrated fungal elements of 45°branching hyphae with positive Periodic Acid-Schiff and Grocott staining.After 3 mo of antifungal therapy,the symptoms,computed tomography scan and bronchoscopy manifestations all showed improvement.CONCLUSION We highlight that clinicians should consider a diagnosis of invasive aspergillosis when radiological examination shows pseudotumor appearance in diabetes mellitus patients.

Correlation of SFRP2 and TPX2 expression with cancer cell apoptosis and EMT process in cervical cancer

Objective: To study the correlation of SFRP2 and TPX2 expression with cancer cell apoptosis and EMT process in cervical cancer. Methods: Patients with cervical cancer who received surgical resection in No.174 Hospital of PLA between June 2015 and December 2016 were selected as the research subjects, moderate amount of cervical cancer lesion and adjacent lesion were collected after surgical resection to extract RNA, and then fluorescent quantitative PCR kit was used to determine the expression of SFRP2, TPX2, apoptosis genes and EMT genes in lesion tissue. Results: SFRP2, SARI, AIF, FHIT, NDRG4, MCPH1 and E-cadherin mRNA expression in cervical cancer lesion were greatly lower than those in adjacent lesions whereas TPX2, SP2, CyclinD1, Piwil2, HERC4, EFEMP1, EZH2, TGF-β1, N-cadherin and Vimentin1 mRNA expression were greatly higher than those in adjacent lesions;SFRP2 mRNA expression in cervical cancer lesion was positively correlated with SARI, AIF, FHIT, NDRG4, MCPH1 and E-cadherin mRNA expression, and negatively correlated with SP2, CyclinD1, Piwil2, HERC4, EFEMP1, EZH2, TGF-β1, N-cadherin and Vimentin1 mRNA expression whereas TPX2 mRNA expression was negatively correlated with SARI, AIF, FHIT, NDRG4, MCPH1 and E-cadherin mRNA expression, and positively correlated with SP2, CyclinD1, Piwil2, HERC4, EFEMP1, EZH2, TGF-β1, N-cadherin and Vimentin1 mRNA expression. Conclusion: The lowly expressed SFRP2 and highly expressed TPX2 in cervical cancer lesions can inhibit the apoptosis of cancer cells and promote the EMT process of cancer cells.

Metabolic Dysfunction-associated Fatty Liver Disease is Associated with Greater Impairment of Lung Function than Nonalcoholic Fatty Liver Disease

Background and Aims:We compared lung function parameters in nonalcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD),and examined the association between lung function parameters and fibrosis severity in MAFLD.Methods:In this cross-sectional study,we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020.All participants received a health check-up including measurement of anthropometric parameters,biochemical variables,liver ultrasonography,and spirometry.The severity of liver disease was assessed by the fibrosis(FIB)-4 score.Results:The prevalence of MAFLD was 20.4%(n=519)and that of NAFLD was 18.4%(n=469).After adjusting for age,sex,adiposity measures,smoking status,and significant alco-hol intake,subjects with MAFLD had a significantly lower predicted forced vital capacity(FVC,88.27±17.60%vs.90.82±16.85%,p<0.05)and lower 1 s forced expiratory volume(FEV1,79.89±17.34 vs.83.02±16.66%,p<0.05)than those with NAFLD.MAFLD with an increased FIB-4 score was significantly associated with decreased lung function.For each 1-point increase in FIB-4,FVC was diminished by 0.507(95%CI:-0.840,-0.173,p=0.003),and FEV1 was diminished by 0.439(95%CI:-0.739,-0.140,p=0.004).The results remained unchanged when the statistical analyses was performed separately for men and women.Conclusions:MAFLD was significantly asso-ciated with a greater impairment of lung function param-eters than NAFLD.