This study aimed to delve deeper into the effects of CRLF3 on the immune microenvironment and the interaction between CRLF3 and ACTR2 in hepatocellular carcinoma (HCC). CRLF3 and ACTR2 in mouse tumor tissues and HepG2 cells were measured by RT-qPCR and Western Blot. The proliferative ability of HepG2 cells was assessed by MTT and colony formation assays, with apoptosis determined by flow cytometry, and migration and invasion quantified by Transwell assay. The apoptosis rate of CD8+ T cells was calculated by flow cytometry, as well as TNF-α and IFN-γ positivity in CD8+ T cells. TNF-α, IFN-γ, and IL-2 were assayed by ELISA. The interaction between CRLF3 and ACTR2 was examined using immunoprecipitation and Western Blot experiments. CRLF3 targeted binding to ACTR2 promoted the proliferative and migratory capacities of HepG2 cells and inhibited apoptosis. Lowering CRLF3 inhibited HCC cell immune escape, with a significant increase in TNF-α and IFN-γ-positive populations in CD8+ T cells, and enhancing ACTR2 significantly mitigated this effect. Lowering CRLF3 inhibited HCC xenografted tumor growth in nude mice. Through its targeted binding to ACTR2, CRLF3 aids in the growth and immune escape of HCC cells.
Metastasis accounts for the vast majority of cancer deaths; however, this complex process has yet to be fully explained. To form metastases, cancer cells must undergo a series of steps, known as the "Metastatic cascade", each of which requires a specific functional transformation. Cancer stem cells (CSCs) play a vital role in tumor metastasis, but their dynamic behavior and regulatory mechanisms have not been fully elucidated. Based on the "Metastatic cascade" theory, this review summarizes the effect of liver CSCs on the metastatic biological programs that underlie the dissemination and metastatic growth of cancer cells. Liver CSCs have the capacity to initiate distant organ metastasis via EMT, and the microenvironment transformation that supports the ability of these cells to disseminate, evade immune surveillance, dormancy, and regenerate metastasis. Understanding the heterogeneity and traits of liver CSCs in these processes is critical for developing strategies to prevent and treat metastasis of advanced hepatocellular carcinoma (HCC).
Cancer stem cells (CSCs) are a group of tumor cells with high tumorigenic ability and self-renewal potential similar to those of normal stem cells. CSCs are the key “seeds” for tumor development, metastasis, and recurrence. A better insight into the key mechanisms underlying CSC survival improves the efficiency of cancer therapy via specific targeting of CSCs. Insulin-like growth factor (IGF)/IGF-1 receptor (IGF-1R) signaling plays an important role in the maintenance of cancer stemness. However, the effect of IGF/IGF-1R signaling on stemness and CSCs and the underlying mechanisms are still controversial. Based on the similarity between CSCs and normal stem cells, this review discusses emerging data on the functions of IGF/IGF-1R signaling in normal stem cells and CSCs and dissects the underlying mechanisms by which IGF/IGF-1R signaling is involved in CSCs. On the other hand, this review highlighted the role of IGF/IGF-1R signaling blockade in multiple CSCs as a potential strategy to improve CSC-based therapy.
Rationale: The interstitial pneumonia (IP) linked to vedolizumab (VDZ) in patients with ulcerative colitis (UC) is rare. Prompt diagnosis and treatment can improve patient outcomes. Patient concerns: A 39-year-old man with UC who received VDZ as sole therapy developed symptoms such as chest tightness, cough, and suffocation. Diagnoses: IP was confirmed through pulmonary function tests, chest computed tomography, and bronchoscopic biopsy. Interventions: The patient was given methylprednisolone and VDZ cessation. Outcomes: The patient’s symptoms improved and remained symptom-free after nearly 2 years. Lessons: VDZ-induced IP should be considered when evaluating pulmonary infections in UC patients treated with VDZ.
为改变医院传统粗放和低效的耗材管理模式,提升医用耗材精细化管理水平,海军第九七一医院通过公开招标方式引入第三方专业物流服务商成立医用耗材供应、管理、配送(supply processing distribution,SPD)运营中心,对医院医用耗材管理流程及管理方式进行改造,配备专业耗材配送管理团队,搭建智能SPD管理系统,在手术室建立智能化库房,协助消毒供应中心进行手术器械消毒工作,为医院高值耗材全流程精准管理提供服务.通过医用耗材SPD模式改造与应用,完成了医院高值耗材的精细化管理,实现了医用耗材供应链全过程质量控制和全流程管理,大幅提高医院整体运营效率,降低运营成本.
目的 开发卫生应急装备物资自动化管理系统,解决目前医疗队应急装备物资主要靠手工管理的落后模式.方法 利用二维码QR code编码技术、数据库管理技术、嵌入式技术等,开发便携式智能扫描及数据管理一体化的卫生装备物资信息管理软硬件系统,通过二维码QR code图形生成、打印、识别,实现对箱组、背囊的快速识别和内装物品点验,对所有库存物资装备的数量、有效期等进行智能化管理.结果 系统大幅提升卫生装备物资清点的准确率及效率,降低劳动强度,同时可实现卫生装备物资的全程追溯及智能管理.结论 系统可用于前出支援医疗队的物资装备智能管理,实时更新、掌握前出医疗队的物资消耗、剩余物资品类状况,及时进行相关决策.
1例26岁女性患者因系统性红斑狼疮、肺动脉高压入院,给予激素、环磷酰胺(cyclophosphamide,CTX)(0. 4 g,每周1次静脉滴注)、羟氯喹,以及呋塞米、螺内酯利尿,地高辛强心,西地那非靶向扩肺血管治疗。2个月后(CTX累积剂量3. 2 g),患者出现丙氨酸氨基转移酶大于800 U/L,停用CTX 1个月后好转。再次行CTX治疗,当CTX累积量达8. 0 g时,患者出现皮肤巩膜黄染等症状,经实验室检查及肝穿刺活检,结果证实为CTX引起的急性淤胆性肝炎,停用CTX 32 d后好转。本文对CTX致该患者的2种形式肝损伤原因进行了分析,并结合文献对CTX引起淤胆性肝炎的病例进行了总结。
TLR3 and IL-10 play a crucial role in antiviral defence. However, there is a controversy between TLR3 rs3775291 and IL-10 rs1800871 polymorphisms and the risk of hepatitis B virus (HBV) infection. The purpose of this study is to explore the relationship between the two single nucleotide mutations and the risk of HBV infection by meta-analysis. Medline, EMBASE, Web of Science, CNKI, China Wanfang database were searched for the case-control studies on the relationship between TLR3 rs3775291 and IL-10 rs1800871 polymorphism and susceptibility to HBV, updated to June 2020. The data were analysed by Stata 15.0 software. A total of 22 articles were included. The results showed that in the analysis of IL10 rs1800871 polymorphism and the risk of HBV infection, the pooled OR was 1.21 (95% CI 1.06-1.37), 1.28 (95% CI 1.04-1.56) and 1.20 (95% CI 1.06-1.37) and 1.40 (95% CI 1.07-1.83) in the allele model (Cvs.T), dominant model (CC+CTvs.TT), recessive model (CCvs.CT+TT) and homozygous model (CCvs.TT), respectively. There was no statistical significance in the heterozygote model. A subgroup analysis of the Asian population showed similar results. The analysis of TLR3 rs3775291 polymorphism and the risk of HBV showed that in the allele model (Tvs.C), the pooled OR was 1.30 (95% CI 1.05-1.61). Except for the recessive model, no significances were found in other genetic models. In conclusion, TLR3 rs3775291 and IL-10 rs1800871 polymorphisms are associated with the risk of HBV. Allele C and genotype CC at IL10 rs1800871 loci, as well as allele T and genotype TT at TLR rs3775291 loci, may increase susceptibility to Hepatitis B infection.
Background: The prevalence of cytomegalovirus in China is high and the infection could result in disastrous consequences. Cellular immunity is the main mechanism for virus controlling. We explored the performance of cytomegalovirus antigen-specific enzyme-linked immunospot assay in patients with different infection states in endemic area. Methods: Twenty-eight patients with reliable results were included in statistical analysis. Peripheral blood mononuclear cells were extracted and were stimulated by cytomegalovirus phosphoprotein 65 or immediate early protein-1 antigen respectively. Spot forming cells (SFCs) were counted to evaluate the cellular immune response elicited by antigens. Results: Spots could be clearly displayed, and evenly dispersed with a clean background. The numbers of SFCs were 0 [0-0], 426 [210-601] and 230 [57-513] for uninfected individuals (n = 7), latently infected patients (n = 11) and actively infected patients (n = 10) respectively, which were statistically different. The number of SFCs stimulated by phosphoprotein 65 was significantly higher than that by immediate early protein-1. Conclusions: The number of SFCs was significantly different among patients with different infection state. The stimulatory effect of phosphoprotein 65 was better than that of immediate early protein-1.
目的:构建传染病现场防控装备体系效能评估模型,对装备体系效能进行评估.方法:根据传染病现场防控的勤务任务构建现场防控装备体系,在对装备进行分类的基础上分别构建每类装备的评估指标体系.采用基于主客观综合权重的模糊综合评价模型对单件装备和装备体系效能进行评估,并选取东部地区某一级疾病预防控制机构装备体系进行实例验证.结果:该评估模型具有较好的可操作性,评估结果有效性较好.经验证该一级疾病预防控制机构装备体系效能评估结果为良.结论:利用该模型对传染病现场防控装备体系进行评估,可发现传染病现场防控装备体系的问题和不足,为传染病防控装备体系建设与研发提供理论依据和决策支持,对提高传染病现场防控保障能力具有重要意义.
Currently available Interferon-gamma release assay cannot reliably differentiate active TB (ATB) from non-active TB (non-ATB). This study aimed to evaluate the diagnostic accuracy of the IFN-gamma/IL-2 FluoroSpot assay, which can simultaneously detect IFN-gamma and IL-2 secretion, for differentiating ATB from non-ATB. 191 suspected ATB patients with positive T-SPOT. TB results were consecutively recruited. 64 (33.5%) participants had ATB, including 22 (34.4%) microbiologically or histologically confirmed TB and 42 (65.6%) clinically diagnosed TB. 119 (62.3%) cases were non-ATB and 8 (4.2%) were clinically indeterminate. After being stimulated with ESAT-6 and CFP-10 antigens, the median frequency and proportion of IFN-gamma +IL-2(-) T cells were significantly higher in the ATB group than the non-ATB group (P < .001). The areas under the ROC curves of IFN-gamma +IL-2(-) T cells were larger than those of total IFN-gamma(+) T cells (0.788 vs. 0.739, p = .323). With a cutoff value of 25 SFCs/250,000 PBMCs for frequency, sensitivity and specificity of this assay were 73.4% and 69.8% respectively. When combining the frequency and proportions of IFN-gamma +IL-2(-) T cells, the sensitivity and specificity were increased to 95.3% in parallel testing and 83.2% in serial testing respectively. In conclusion, IFN-gamma/IL-2 FluoroSpot assay is conducive for the diagnosis of ATB in patients with positive T-SPOT. TB results.
Objective The aim of this study was to evaluate the diagnostic performance of T-SPOT.TB for tuberculous lymphadenitis. Methods Suspected tuberculous lymphadenitis patients between September 2010 and September 2018 who had both peripheral blood T-SPOT.TB test and lymph node biopsy were retrospectively enrolled in this study. The cutoff value of T-SPOT.TB test for peripheral blood was set as 24 spot forming cell (SFC)/10 6 periphreral blood monocyte cell (PBMC) according to the instruction of testing kits. The gold standard for diagnosis of TBL was the combination of microbiology results, histopathology results and patient's response to anti-TB treatment. Diagnostic efficacy of T-SPOT.TB was evaluated, including sensitivity, specificity, accuracy, predictive values, and likelihood ratio. Results Among 91 patients who met the inclusion criteria, we excluded 8 cases with incomplete clinical information and 6 cases who lost to follow-up. According to the gold standard, there were 37 cases of true TBL (9 confirmed TBL and 28 probable TBL), 30 cases of non-TBL, and 10 cases of clinically indeterminate diagnosis who were excluded from the final analyses. The T-SPOT.TB tests yielded 43 cases of positive response and 24 cases of negative response. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of peripheral blood T-SPOT.TB for diagnosing TBL were 89.2%, 66.7%, 79.1%, 76.7%, 83.3%, 2.68 and 0.16, respectively. The number of SFCs of T-SPOT.TB in TBL patients [432(134-1264)/10 6 PBMCs] was higher than that in non-TBL patients [0 (0-30) /10 6PBMCs] with a significant difference (Z=-5.306, P <0.001).Conclusion T-SPOT.TB is a rapid and simple diagnostic test for TBL with a high sensitivity and negative predictive value.
Objective To establish an infectious disease field prevention and control equipment system to facilitate equipment efficacy evaluation. Methods The equipment system was determined by analyses on the main procedure of infectious disease field prevention and control,researches on the missions and equipment requirements of grades of facilities for disease prevention and control,references to related equipment allocation standards as well as expert consulting.Results The first-grade system consisted of six classes and 136 subclasses of equipment,the second-grade system was made up of six classes and 114 subclasses of equipment and the third-grade system included six classes and 58 subclasses of equipment. Conclusion The three-grade infectious disease field prevention and control equipment system contributes to equipment efficacy evaluation.
Objective To summarize and analyze the dynamic change of HBsAg levels in patients with chronic Hepatitis B (CHB) after receiving nucleos(t)ide analogues (NAs) as antiviral treatment.Methods Patients who were performed quantitative Hepatitis B surface antigen(qHBsAg) from July 30, 2012 to December 30,2016 in Peking Union Medical College Hospital were retrospectively enrolled.qHBsAg, HBV DNA, HBeAg were collected and analyzed at baseline and at 192-week follow-up every 24 weeks.qHBsAg and HBeAg were assessed with chemiluminesent microparticle immuno assay(CMIA).HBV DNA was assessed with PCR and COBAS Amplicor.Results 60 patients were included.Patients in HBeAg-positive group had higher HBV DNA than that in HBeAg-negative group (P<0.05)at baseline and the two groups both were under detection limit after 48 weeks.BaselineqHBsAg in HBeAg positive-group and negative-group were (3.43±0.73) log10 IU/mL, (3.08±0.47) log10 IU/mL respectively.qHBsAg in HBeAg-positive group was higher than that in HBeAg negative-group on all follow-ups(P<0.05) except 48weeks.However on 168 weeks and 192 weeks, difference between the two groups was statistically significant(P<0.05).In HBeAg-positive group,quantitative HBeAg dropped significantly during antiviral treatment.Conclusions HBV replication can be suppressed in the process of long-term NAs treatment in CHB patients.However qHBsAg decline is not so obvious, which indicates that HBsAg cleavence is difficult,and long-term NAs therapy is still necessary.
The diagnostic values of interferon-gamma release assays (IGRA) in tuberculous lymphadenitis (TBL) vary a lot in different research. We conducted a retrospective study to evaluate the diagnostic performance of T-SPOT.TB for suspected tuberculous lymphadenitis (TBL) patients. Suspected tuberculous lymphadenitis patients with both T-SPOT.TB on peripheral blood mononuclear cells (PBMCs) and lymph node biopsy pathology were retrospective enrolled in this study from Peking Union Medical College Hospital (PUMCH) between September 2010 and December 2014. T-SPOT.TB results were evaluated against patients’ final diagnosis of TBL which was made based on clinical manifestations, radiology, microbiological and histopathological evaluation, and response to anti-TB treatment. The sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB were analyzed. Among the 52 patients enrolled, 5 confirmed TBL, 18 probable TBL and 16 non-TB were diagnosed respectively. 3 patients lost of follow up and 10 patients with clinically indeterminate diagnosis were not included in the final analysis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of T-SPOT.TB on PBMCs for diagnosing TBL were 95.7% (76.0%–99.8%); 75.0% (47.4%–91.7%), 84.6% (64.3%–95.0%), 92.3% (62.1%–99.6%), 3.826 (1.630–8.980), 0.058 (0.008–0.411) for T-SPOT.TB, respectively. Frequencies of spot forming cells (SFCs) of T-SPOT.TB were [526 (151–1248)/106 PBMCs] in TBL patients compared with [96 (34–674)/106 PBMCs] in non-TB patients, and no statistical difference was attained (P = 0.150). The best T-SPOT. TB cutoff value for TBL is 32 SFCs/106 PBMCs according to ROC curve, with the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) being 91.3% (70.5%–98.5%), 81.3% (53.7%–95.0%), 87.5% (66.5%–96.7%), 86.7%(58.4%-97.7%), 4.870(1.742–13.609), 0.107(0.028–0.414) respectively. T- SPOT.TB on PBMCs might be a rapid and accurate diagnostic test for TBL, with a high sensitivity and negative predictive value. All authors: No reported disclosures.
目的:观察并比较替比夫定、阿德福韦酯联用与恩替卡韦单药治疗失代偿期乙型肝炎(乙肝)肝硬化的疗效。方法失代偿期乙肝肝硬化患者94例,随机分为联合组与单药组各47例。联合组口服替比夫定(600 mg/d)和阿德福韦酯(10 mg/d),单药组口服恩替卡韦(0.5 mg/d),两组疗程均为48周。分别于治疗12、24、48周时进行肝功能相关指标检测、Child-Pugh分级、计算HBV DNA转阴率及HBeAg血清学转换率,观察并记录HBV耐药及药物不良反应发生情况。结果联合组、单药组在治疗48周时,血清总胆红素( TBIL)、ALT、白蛋白( ALB)、凝血酶原活动度(PTA)水平及Child-Pugh评分均较治疗前好转(P均<0.05),两组治疗后差异无统计学意义。治疗12、24、48周时,联合组与单药组HBV DNA转阴率、HBeAg血清学转换率差异均无统计学意义。两组治疗过程中均未出现病毒学突破或严重不良反应。结论替比夫定、阿德福韦酯联用与恩替卡韦单药治疗失代偿期乙肝肝硬化均可有效抑制病毒复制,减少耐药发生,但联合用药效果并不优于单药治疗。
Objective To provide important references and DSS for allocation and evaluation of field infectious disease prevention and control equipment.Methods With the deployment of C# language, an effectiveness evaluation system was developed based on Microsoft Visual Studio, which mainly consisted of the basic data layer, data processing layer and user operation layer.Results This easy-to-operate and user-friendly system demonstrated its consistency with the actual calculation results in performance tests using typical equipment data, which indicated its advantages in meeting the requirements of equipment effectiveness evaluation. Conclusion With adoption of scientific evaluation indexes and methodology, the system could provide objective evaluation results.
Objective To study the support capability assessment and type selection by establishing an assessment index system for infectious disease protection equipment. Methods literature inquiry, investigation and the grey comprehensive evaluation method were involved in this study. Results The concept, classification, index system and assessment method of infectious disease protection equipment were determined. Conclusion Some profiles of the system for infectious disease protection equipment are put forward to lay a foundation for further research, including the support capability assessment index system, evaluation method.
Objective:To investigate the effects and its significance of survivin gene in rat liver regeneration after partial hepatectomy.Methods:Wister rat liver regeneration model of 70% partial hepatectomy was established.The expressions of Survivin and cell cycle-related protein cyclinD1 were detected by immunohistochemistry in liver regeneration rat tissues at different time points.Results:The level of Survivin protein expression was significantly increased during 12~72 h after partial hepatectomy and reached its peak at 48 h after partial hepatectomy.The level of cyclinD1 was upregulated at 12,24,48 h,and 72 h after partial hepatectomy and highly correlated with survivin protein level.Conclusion:The high expression of Survivin protein is significantly correlated with the liver regeneration after partial hepatectomy.
Objective To investigate the expression of RECK and MMP-9 in pancreatic cancer and to explore the relationship between RECK, MMP-9 expression and the clinicopathological characteristics.Methods PV6000 immunohistochemical method was used to detect the expression of RECK and MMP-9 in 28 cases of pancreatic cancer and 10 cases of normal pancreatic tissue. All the statistical analyses were performed by using SPSS 13.0 statistical software to determine the relationship between RECK, MMP-9 expression and the clinicopathological characteristics. Results The overall positive rate of RECK espression was 46.43% (13/28)in pancreatic cancer, which was significantly lower than that in normal pancreatic tissue (90%, 9/10). The positive rate of RECK espression in Ⅰ + Ⅱ clinical stage (75.0% ,9/12) was significantly higher than that in Ⅲ + Ⅳ stage (25.0%, 4/16 P < 0.05 ). The positive rate of RECK expression in cases without distant metastases (60.0%, 12/60) was significantly higher than that in cases with distant metastasis (12.5%, 1/8,P<0.05). The overall positive rate of MMP-9 was 75% (21/28) in pancreatic cancer, and 20% (2/10) in normal pancreatic tissue. The comparison between these two groups indicated a significant difference (P <0.01 ). The positive rate of MMP-9 in Ⅰ + Ⅱ clinical stage(50.0% ,6/12) was significantly lower than that in Ⅲ + Ⅳ stage (93.8,15/16, P < 0.05). The positive rate of MMP-9 in well differentiation group(33.3%,1/3 ) was significantly lower than that in poor differentiation group ( 100%, 12/12 ,P < 0. 01 ). The expressionof RECK was negatively correlated with the expression of MMP-9 ( r = - 0. 536, P < 0.01 ). Conclusions RECK is lowly expressed in pancreatic cancer, but MMP-9 is highly expressed. RECK and MMP-9 may serve as important markers in the evaluation of tumor stage.