Comprehensive understanding of glioblastoma molecular phenotypes:classification,characteristics,and transition

Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide.In precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward therapy.Deep understanding of the different molecular expression patterns of GBM subtypes is critical.Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes.The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors.These subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard therapy.Herein,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype.Furthermore,we review the mesenchymal transition mechanisms of GBM under various regulators.

Identification of clinical subphenotypes of sepsis after laparoscopic surgery

Objective:Some patients exhibit septic symptoms following laparoscopic surgery,leading to a poor prognosis.Effective clinical subphenotyping is critical for guiding tailored therapeutic strategies in these cases.By identifying predisposing factors for postoperative sepsis,clinicians can implement targeted interventions,potentially improving outcomes.This study outlines a workflow for the subphenotype methodology in the context of laparoscopic surgery,along with its practical application.Methods:This study utilized data routinely available in clinical case systems,enhancing the applicability of our findings.The data included vital signs,such as respiratory rate,and laboratory measures,such as blood sodium levels.The process of categorizing clinical routine data involved technical complexities.A correlation heatmap was used to visually depict the relationships between variables.Ordering points were used to identify the clustering structure and combined with Consensus K clustering methods to determine the optimal categorization.Results:Our study highlighted the intricacies of identifying clinical subphenotypes following laparoscopic surgery,and could thus serve as a valuable resource for clinicians and researchers seeking to explore disease heterogeneity in clinical settings.By simplifying complex methodologies,we aimed to bridge the gap between technical expertise and clinical application,fostering an environment where professional medical knowledge is effectively utilized in subphenotyping research.Conclusion:This tutorial could primarily serve as a guide for beginners.A variety of clustering approaches were explored,and each step in the process contributed to a comprehensive understanding of clinical subphenotypes.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes

●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited.Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients’medical records.A hierarchical cluster analysis was performed.The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts.●RESULTS:A total of 164 children(299 eyes)were divided into two clusters based on their ocular features.Cluster 1(96 eyes)had a shorter axial length(mean±SD,19.44±1.68 mm),a low prevalence of macular abnormalities(1.04%),and no retinal abnormalities or posterior cataracts.Cluster 2(203 eyes)had a greater axial length(mean±SD,20.42±2.10 mm)and a higher prevalence of macular abnormalities(8.37%),retinal abnormalities(98.52%),and posterior cataracts(4.93%).Compared with the eyes in Cluster 2(57.14%),those in Cluster 1(71.88%)had a 2.2 times higher chance of good best-corrected visual acuity[<0.7 logMAR;OR(95%CI),2.20(1.25–3.81);P=0.006].●CONCLUSION:This retrospective study categorizes congenital cataracts into two distinct clusters,each associated with a different likelihood of visual outcomes.This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit,thereby making strides toward precision medicine in the field of congenital cataracts.

Association between the Different Phenotypes of Polycystic Ovary Syndrome and the Outcome in in Vitro Fertilization at Human Reproductive Center Paul et Chantal Biya-Yaoundé

Background: In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) represents the final step in the management of Polycystic Ovarian Syndrome (PCOS). Our objective was to study the association between PCOS phenotypes and IVF/ICSI results in women admitted to Gynaecological Endoscopic Surgery and Human Reproductive Teaching Hospital (CHRACERH). Material and Method: We carried out a cohort study with historical-prospective data collection over a period of seven years (January 2016 to March 2023) at Chracerh. PCOS patients were subdivided into 4 subgroups A, B, C and D. Results: We recruited 128 patients including 64 PCOS patients divided into four phenotypes and 64 non-PCOS patients constituting the control group. Phenotype D without hyperandrogenism had used the lowest dose of gonadotropins, i.e. 1939.7 ± 454.3 IU, and had produced a greater quantity of estradiol on the day ovulation was triggered (6529.8 ± 4324.8 ng/ml). The average number of punctured follicles and mature oocytes were higher in the phenotype D group. Ovarian hyperstimulation syndrome (OHSS) occurred mainly in phenotype D (3/35), with an estimated prevalence of 2.3%. The fertilization rate seemed lower in the hyperandrogenic phenotypes A, B, C compared to the group without hyperandrogenism without significant difference (p = 0.461). The biological pregnancy rate and live birth rate were comparable between the different groups. Conclusion: Phenotype D used less dose of gonadotropins. Biological pregnancy and live birth rates were comparable between the different phenotypes.

Phenotypic Detection of Enterobacterales Strains Susceptible of Producing OXA-48 Carbapenemase

Background: Nowadays, emergence of Carbapenemase-Producing Enterobacterales (CPE) throughout the world has become a public health problem, especially in countries with limited resources. In recent years, CPE of type OXA-48 (Ambler class D) have been identified in Dakar. The aim of this study was to evaluate the phenotypic detection of OXA-48 CPE using a temocillin disc (30 μg). Methodology: A retrospective study was carried out at Medical Biology Laboratory of Pasteur Institute in Dakar on Ertapenem-Resistant Enterobacterales (ERE) strains isolated from 2015 to 2017. These strains were then tested with a 30 μg temocillin disc. Any strain resistant to temocillin (inhibition diameter Results: Forty-one ERE isolated during the study period were tested, of which 34 (82.9%) were OXA-48 based on phenotypic detection using temocillin disc and confirmed by PCR (100%). OXA-48 CPE strains detected were composed of Klebsiella pneumoniae (n = 14;41.2%), Enterobacter cloacae (n = 8;23.5%), Escherichia coli (n = 7, 20.5%), Citrobacter freundii (n = 3;8.8%), Cronobacter sakazakii (n = 1;3%) and Morganella morganii (n = 1;3%). Conclusion: Temocillin resistance has a good positive predictive value for detecting OXA-48 CPE by phenotypic method, confirmed by PCR. Temocillin is therefore a good marker for detection of OXA-48 CPE except Hafnia alvei.

Phenotypic Characterization and QTL/Gene Identification for Internode Number and Length Related Traits in Maize

Internode number and length are the foundation to constitute plant height, ear height and the above-ground spatial structure of maize plant. In this study, segregating populations were constructed between EHel with extremely low ear height and B73. Through the SNP-based genotyping and phenotypic characterization, 13 QTL distributed on the chromosomes (Chrs) of Chr1, Chr2, Chr5-Chr8 were detected for four traits of internode no. above ear (INa), average internode length above ear (ILaa), internode no. below ear (INb), and average internode length below ear (ILab). Phenotypic variation explained (PVE) by a single QTL ranged from 6.82% (qILab2-2) to 12.99% (qILaa5). Zm00001d016823 within the physical region of qILaa5, the major QTL for ILaa with the largest PVE was determined as the candidate through the genomic annotation and sequence alignment between EHel and B73. Product of Zm00001d016823 was annotated as a WEB family protein homogenous to At1g75720. qRT-PCR assay showed that Zm00001d016823 highly expressed within the tissue of internode, exhibiting statistically higher expression levels among internodes of IN4 to IN7 in EHel than those in B73 (P Zm00001d016823 might provide novel insight into molecular mechanism beyond phytohormones controlling internode development in maize.

SPP-extractor:Automatic phenotype extraction for densely grown soybean plants

Automatic collecting of phenotypic information from plants has become a trend in breeding and smart agriculture.Targeting mature soybean plants at the harvesting stage,which are dense and overlapping,we have proposed the SPP-extractor(soybean plant phenotype extractor)algorithm to acquire phenotypic traits.First,to address the mutual occultation of pods,we augmented the standard YOLOv5s model for target detection with an additional attention mechanism.The resulting model could accurately identify pods and stems and could count the entire pod set of a plant in a single scan.Second,considering that mature branches are usually bent and covered with pods,we designed a branch recognition and measurement module combining image processing,target detection,semantic segmentation,and heuristic search.Experimental results on real plants showed that SPP-extractor achieved respective R^(2) scores of 0.93–0.99 for four phenotypic traits,based on regression on manual measurements.

What Impact on Phenotype for Patients with Karyotype 46, XX DSD SRY Positive at CHU Dantec in Senegal: About 5 Cases?

Background: In disorders of sexual differentiation, sexual development may not conform to the chromosomal structure, thus forming different types of abnormalities. Among these abnormalities is syndrome 46, XX DSD where most patients are female phenotype with clitoral hypertrophy that can go to complete masculinization especially in the presence of the SRY gene. Objective: The goal of this work is to demonstrate a relationship between the genotype and the phenotype in five patients karyotype 46, XX with the presence of the SRY gene. Methodology: The study involves five patients referred to the laboratory under suspicion of sexual development anomalies. The diagnosis took place through hormonal and echography examinations, a classic cytogenetic study (Barr chromatin and karyotype) and an amplification of the SRY gene located on the Y chromosome. The resulting PCR products were sent for sequencing. Results: Based on the results of clinical and paraclinical tests carried out it was found clitoral hypertrophy, the presence of clitoris penis for some, presence of normal penis for others. In addition, echography revealed a lack of female internal genitalia (P2, P3), and a presence of testicles (P3, P4, P5). Genetic analysis (chromosomal and molecular) showed a karyotype 46, XX SRY (+) for all patients. New mutations were found c.246 T > A, p.82 Asn82Lys and c.171 G > C, p.57 Gln57His. Conclusion: In our study, we were able to correlate each DSD with karyotype 46, XX to a pathology such as 46, XX DSD testicular, 46, XX DSD with clitoral hypertrophy and ovotestis 46, XX. The next step will undoubtedly be the integration of other molecular techniques (genotyping, FISH, CGH or even the CGH array) to further genetic exploration.

Identification of tolerance to high density and lodging in short petiolate germplasm M657 and the effect of density on yield-related phenotypes of soybean

Soybean yield has traditionally been increased through high planting density,but investigating plant height and petiole traits to select for compact architecture,lodging resistance,and high yield varieties is an underexplored option for further improving yield.We compared the relationships between yield-related traits,lodging resistance,and petioleassociated phenotypes in the short petiole germplasm M657 with three control accessions during 2017–2018 in four locations in the Huang–Huai region,China.The results showed that M657 exhibited stable and high tolerance to high planting density and resistance to lodging,especially at the highest density(8×105 plants ha–1).The regression analysis indicated that a shorter petiole length was significantly associated with increased lodging resistance.The yield analysis showed that M657 achieved higher yields under higher densities,especially in the northern part of the Huang–Huai region.Among the varieties,there were markedly different responses to intra-and inter-row spacing designs with respect to both lodging and yield that were related to location and density.Lodging was positively correlated with planting density,plant height,petiole length,and number of effective branches,but negatively correlated with stem diameter,seed number per plant,and seed weight per plant.The yield of soybean was increased by appropriately increasing the planting density on the basis of the current soybean varieties in the Huang–Huai region.This study provides a valuable new germplasm resource for the introgression of compact architecture traits that are amenable to providing a high yield in high density planting systems,and it establishes a high-yield model of soybean in the Huang–Huai region.

Coexistent alcohol-related cirrhosis and chronic pancreatitis have a comparable phenotype to either disease alone:A comparative retrospective analysis

BACKGROUND Alcohol use disorder is a prevalent disease in the United States.It is a well-demonstrated cause of recurrent and long-standing liver and pancreatic injury which can lead to alcohol-related liver cirrhosis(ALC)and chronic pancreatitis(ACP).ALC and ACP are associated with significant healthcare utilization,cost burden,and mortality.The prevalence of coexistent disease(CD)ranges widely in the literature and the intersection between ALC and ACP is inconsistently charac-terized.As such,the clinical profile of coexistent ALC and ACP remains poorly understood.We hypothesized that patients with CD have a worse phenotype when compared to single organ disease.AIM To compare the clinical profile and outcomes of patients with CD from those with ALC or ACP Only.METHODS In this retrospective comparative analysis,we reviewed international classi-fication of disease 9/10 codes and electronic health records of adult patients with verified ALC Only(n=135),ACP Only(n=87),and CD(n=133)who received care at UPMC Presbyterian-Shadyside Hospital.ALC was defined by histology,imaging or clinical evidence of cirrhosis or hepatic decompensation.ACP was defined by imaging findings of pancreatic calcifications,moderate-severe pancreatic duct dilatation,irregularity or atrophy.We compared demographics,pertinent clinical variables,healthcare utilization,and mortality for patients with CD with those who had single organ disease.RESULTS Compared to CD or ACP Only,patients with ALC Only were more likely to be older,Caucasian,have higher body mass index,and Hepatitis B or C infection.CD patients(vs ALC Only)were less likely to have imaging evidence of cirrhosis and portal hypertension despite possessing similar MELD-Na and Child C scores at the most recent contact.CD patients(vs ACP Only)were less likely to have acute or recurrent acute pancreatitis,diabetes mellitus,insulin use,oral pancreatic enzyme therapy,and need for endoscopic therapy or pancreatic surgery.The number of hospitalizations in patients with CD were similar to ACP Only but significantly higher than ALC Only.The overall mortality in patients with CD was similar to ALC Only but trended to be higher than ACP Only(P=0.10).CONCLUSION CD does not have a worse phenotype compared with single organ disease.The dominant phenotype in CD is similar to ALC Only which should be the focus in longitudinal follow-up.

Redefying the therapeutic strategies against cardiorenal morbidity and mortality:Patient phenotypes

Chronic kidney disease(CKD)patients face an unacceptably high morbidity and mortality,mainly from cardiovascular diseases.Diabetes mellitus,arterial hypertension and dyslipidemia are highly prevalent in CKD patients.Established therapeutic protocols for the treatment of diabetes mellitus,arterial hypertension,and dyslipidemia are not as effective in CKD patients as in the general population.The role of non-traditional risk factors(RF)has gained interest in the last decades.These entail the deranged clinical spectrum of secondary hyperparathyroidism involving vascular and valvular calcification,under the term“CKDmineral and bone disorder”(CKD-MBD),uremia per se,inflammation and oxidative stress.Each one of these non-traditional RF have been addressed in various study designs,but the results do not exhibit any applied clinical benefit for CKD-patients.The“crusade”against cardiorenal morbidity and mortality in CKD-patients is in some instances,derailed.We propose a therapeutic paradigm advancing from isolated treatment targets,as practiced today,to precision medicine involving patient phenotypes with distinct underlying pathophysiology.In this regard we propose two steps,based on current stratification management of corona virus disease-19 and sepsis.First,select patients who are expected to have a high mortality,i.e.,a prognostic enrichment.Second,select patients who are likely to respond to a specific therapy,i.e.,a predictive enrichment.

LncRNA CACNA1G-AS1 up-regulates FTH1 to inhibit ferroptosis and promote malignant phenotypes in ovarian cancer cells

Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.

A novel phenotype of B cells associated with enhanced phagocytic capability and chemotactic function after ischemic stroke

Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45.Macrophage-like B cells chara cterized by co-expression of B-cell and macrophage markers,showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes.Gene Ontology analysis found that the expression of genes associated with phagocytosis,including phagosome-and lysosome-related genes,was upregulated in macrophage-like B cells.The phagocytic activity of macrophage-like B cells was ve rified by immunostaining and three-dimensional reconstruction,in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia.Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways.Single-cell RNA sequencing showed that the transdiffe rentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP fa mily to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage.Furthermore,this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury,Alzheimer’s disease,and glioblastoma.Overall,these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain.These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.

Role of Cyclin D1b in Inducing Macrophages Toward a Tumor-associated Macrophage-like Phenotype in Murine Breast Cancer

Objective:Tumor-associated macrophages(TAMs)of the M2 phenotype are frequently associated with cancer progression.Invasive cancer cells undergoing epithelial-mesenchymal transition(EMT)have a selective advantage as TAM activators.Cyclin D1b is a highly oncogenic splice variant of cyclin D1.We previously reported that cyclin D1b enhances the invasiveness of breast cancer cells by inducing EMT.However,the role of cyclin D1b in inducing macrophage differentiation toward tumor-associated macrophage-like cells remains unknown.This study aimed to explore the relationship between breast cancer cells overexpressing cyclin Dlb and TAMs.Methods:Mouse breast cancer 4T1 cells were transfected with cyclin D1b variant and co-cultured with macrophage cells in a Transwell coculture system.The expression of characteristic cytokines in differentiated macrophages was detected using qRT-PCR,ELISA and zymography assay.Tumor-associated macrophage distribution in a transplanted tumor was detected by immunofluorescence staining.The proliferation and migration ability of breast cancer cells was detected using the cell counting kit-8(CCK-8)assay,wound healing assay,Transwell invasion assay,and lung metastasis assay.Expression levels of mRNAs were detected by qRT-PCR.Protein expression levels were detected by Western blotting.The integrated analyses of The Cancer Genome Atlas(TCGA)datasets and bioinformatics methods were adopted to discover gene expression,gene coexpression,and overall survival in patients with breast cancer.Results:After co-culture with breast cancer cells overexpressing cyclin D1b,RAW264.7 macrophages were differentiated into an M2 phenotype.Moreover,differentiated M2-like macrophages promoted the proliferation and migration of breast cancer cells in turn.Notably,these macrophages facilitated the migration of breast cancer cells in vivo.Further investigations indicated that differentiated M2-like macrophages induced EMT of breast cancer cells accompanied with upregulation of TGF-β1 and integrinβ3 expression.Conclusion:Breast cancer cells transfected with cyclin D1b can induce the differentiation of macrophages into a tumor-associated macrophage-like phenotype,which promotes tumor metastasis in vitro and in vivo.

钢渣/氮掺杂改性活性炭催化过硫酸盐降解罗丹明B

以提高钢渣资源化利用和深度降解有机污染物为研究目标,通过改变氨气煅烧温度制备了系列钢渣/氮掺杂改性活性炭复合材料,并用于催化过硫酸钠处理罗丹明B(RhB)废水。同时采用N2吸附/脱附、XRD、XPS等手段对复合材料的孔结构和表面性质进行了表征。结果表明:氮元素的引入可改善复合材料中活性金属与活性炭之间的相互作用,从而提高复合材料的催化活性。以最优复合材料60%GZ/AC-N800为研究对象,在反应温度为35℃、PS加量为2 g/L和宽pH(3~11)操作条件下,反应30 min后罗丹明B(100 mg/L)的去除率可达88.7%~92.2%。动力学分析发现,60%GZ/AC-N800复合材料催化PS降解RhB符合准二级动力学。自由基掩蔽实验发现,该降解过程是自由基途径(SO_(4)^(·-)和·OH)和非自由基途径(^(1)O_(2))共同参与反应的氧化过程。

淫羊藿苷调控mTOR/Akt/CREB通路对高糖诱导的足细胞自噬及凋亡的影响

目的 探讨淫羊藿苷对高糖诱导的足细胞自噬、凋亡及哺乳动物雷帕霉素靶蛋白(mTOR)/丝氨酸苏氨酸蛋白激酶(Akt)/环磷酸腺苷反应元件结合蛋白(CREB)通路的影响。方法 将小鼠足细胞MPC5分为5组:正常对照组(5.5 mmol·L^(-1)葡萄糖)、高糖组(30 mmol·L^(-1)葡萄糖)、淫羊藿苷组(30 mmol·L^(-1)葡萄糖+5μmol·L^(-1)淫羊藿苷)、GDC-0349组(30 mmol·L^(-1)葡萄糖+50μmol·L^(-1)GDC-0349)、淫羊藿苷+GDC-0349组(30 mmol·L^(-1)葡萄糖+5μmol·L^(-1)淫羊藿苷+50μmol·L^(-1)GDC-0349)。培养48 h后,噻唑蓝法检测MPC5细胞活力;吖啶橙染色观察MPC5细胞自噬情况;流式细胞术检测MPC5细胞凋亡;蛋白印迹法检测MPC5细胞自噬[微管相关蛋白1轻链3(LC3)Ⅱ、LC3Ⅰ、自噬相关蛋白(Beclin-1)]、凋亡[Bcl-2相关X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)]和mTOR/Akt/CREB通路相关蛋白的表达。结果 与正常对照组比较,高糖组MPC5细胞活力、Bcl-2、磷酸化mTOR(p-mTOR)/mTOR、磷酸化Akt(p-Akt)/Akt、磷酸化CREB(p-CREB)/CREB蛋白表达水平显著降低(P<0.05),自噬能力增强,自噬体表现出橙色荧光,细胞凋亡率、LC3Ⅱ/LC3Ⅰ、Beclin-1、Bax蛋白表达水平显著升高(P<0.05)。与高糖组比较,淫羊藿苷组MPC5细胞活力、LC3Ⅱ/LC3Ⅰ、Beclin-1、Bcl-2、p-mTOR/mTOR、p-Akt/Akt、p-CREB/CREB蛋白表达水平显著升高,自噬能力进一步增强,自噬体数量增多,自噬体呈现出砖红色荧光(P<0.05),细胞凋亡率、Bax蛋白表达水平显著降低(P<0.05);GDC-0349组MPC5细胞活力、LC3Ⅱ/LC3Ⅰ、Beclin-1、Bcl-2、p-mTOR/mTOR、p-Akt/Akt、p-CREB/CREB蛋白表达水平显著降低,自噬能力减弱,自噬体数量减少,自噬体表现出橙色荧光(P<0.05),细胞凋亡率、Bax蛋白表达水平显著升高(P<0.05);淫羊藿苷+GDC-0349可逆转淫羊藿苷对高糖诱导MPC5细胞的作用效果(P<0.05)。结论 淫羊藿苷通过激活mTOR/Akt/CREB通路促进高糖诱导的足细胞自噬抑制细胞凋亡。

慢性乙型肝炎患者血清HBsAg与单个核细胞乙型肝炎病毒RNA水平对聚乙二醇干扰素治疗效果的预测价值

目的探讨慢性乙型肝炎患者外周血清HBsAg、乙型肝炎病毒(HBV)DNA与血清HBV RNA及单个核细胞(PBMC)HBV RNA的关系。方法50例慢性乙型肝炎患者,给予Peg-IFNα-2b 180μg皮下注射,每周一次,分别在初始治疗、24周和48周,检测患者血清HBV五项、肝功能、HBV DNA、HBV RNA及PBMC中HBV RNA的变化。结果患者三个时间段的生化指标ALT、AST、TBIL、AKP及GGT比较差异无统计学意义(P>0.05);免疫学标志物HBsAg、HBsAb、HBeAg、HBeAb差异有统计学意义(P<0.05);血清HBV DNA及HBV RNA与PBMC HBV RNA差异有显著统计学意义(P<0.001)。结论Peg-IFNα-2b抗病毒治疗各时间段,肝功能转氨酶无显著变化;治疗24周,血HBsAg、HBV DNA与HBV RNA及PBMC HBV RNA快速下降,有显著相关性;治疗48周,血清HBsAg、HBV DNA与HBV RNA及PBMC HBV RNA相关性减弱。因此,24周HBV RNA下降幅度优于48周,更能预测临床治愈。

高迁移率族蛋白B1对树突状细胞表型、吞噬功能及ERK/JNK/P38 MAPK信号通路的影响

目的探究高迁移率族蛋白B1(high mobility group box 1,HMGB1)对硫酸吲哚酚(indoxyl sulfate,IS)诱导的树突状细胞(DCs)表型、吞噬功能及细胞外信号调节激酶(ERK)/氨基末端蛋白激酶(JNK)/丝裂原活化蛋白激酶P38抗体(P38 MAPK)信号通路的影响。方法分别以30、300、600μmol·L^(-1)IS干预人原代DC细胞24 h,分为Control组、IS-30组、IS-300组、IS-600组,通过流式细胞分析鉴定细胞表型并检测细胞吞噬功能;细胞经600μmol·L^(-1)IS干预24 h后加入1 mg·L^(-1)anti-HMGB1或经1 mg·L^(-1)HMGB1单独处理后分为Control组、IS组、HMGB1组、IS^(+)anti-HMGB1组,通过流式细胞分析鉴定细胞表型并检测细胞吞噬功能;Western blot和免疫荧光染色检测ERK/JNK/P38 MAPK信号通路相关蛋白表达。结果随IS浓度增加,CD83^(+)和CD86^(+)细胞数逐渐增加(P<0.01),DCs吞噬能力逐渐下降(P<0.01);与IS组相比,IS^(+)anti-HMGB1组的CD83^(+)和CD86^(+)细胞数明显减少(P<0.01),细胞吞噬能力增加(P<0.01)。此外,与Control组比较,IS或HMGB1组p-ERK/ERK、p-P38/P38、p-JNK/JNK的蛋白表达升高(均P<0.01);与IS组相比,IS^(+)anti-HMGB1组p-ERK/ERK、p-p38/p38、p-JNK/JNK的蛋白表达降低(均P<0.01)。结论拮抗HMGB1可抑制IS诱导的DCs表型及成熟并抑制ERK/JNK/P38 MAPK信号通路激活。

基于线粒体Cyt b基因序列的4个黄尾鲴养殖群体遗传多样性分析

黄尾鲴(Xenocypris davidi)是浙江省自然水域增殖放流的主要鱼类,为了解人工繁育对黄尾鲴遗传多样性的影响,利用线粒体DNA细胞色素b基因(Cyt b)对4个养殖群体的遗传多样性进行研究,旨在为黄尾鲴增殖放流策略制定和实施提供基础数据。结果显示,在编码Cyt b的1 140 bp序列中,检测到157个变异位点,界定了21种单倍型,其中长兴、双浦、八里店和醴陵群体的单倍型数目分别为10个、11个、7个和2个,单倍型多样性介于0.226~0.794,核苷酸多样性介于0.006 14~0.023 86。除醴陵群体遗传多样性较低外,其余3个养殖群体的遗传多样性具有高单倍型数和高核苷酸多样性的特点。4个黄尾鲴养殖群体间的遗传距离为0.018 74~0.092 74,遗传分化指数为0.808 63(P<0.01),其中长兴和八里店群体的分化程度较低,双浦和醴陵群体的分化程度较高,且遗传变异主要发生在群体间。本研究结果可从分子水平为黄尾鲴的资源保护和人工增殖放流提供参考依据。

以皮肤肿块为首发临床表现的伴MYC和BCL2重排弥漫性大B细胞淋巴瘤

报告1例以皮肤肿块为首发临床表现的伴细胞性骨髓细胞瘤病病毒癌(MYC)基因和B细胞淋巴瘤因子2(BCL2)基因重排弥漫性大B细胞淋巴瘤。患者女,87岁。左侧眉弓上方皮肤结节1年。皮肤科检查:左眉上方一肤色圆形肿物,隆起于皮肤表面,肿物表面可见浸润性红斑,伴少许渗出,并见结痂、鳞屑,边界清楚。皮损组织病理检查:表皮形态正常,真皮层内大量母细胞样淋巴细胞结节状浸润。免疫组化:母细胞样淋巴细胞CD45、CD79a、B细胞淋巴瘤因子6(BCL6)、细胞周期蛋白D1(cyclin D1)及MYC均(+);CD3、CD2、CD30、细胞角蛋白(CKP)、间变性淋巴瘤激酶(ALK)及Epstein-Barr病毒编码RNA(EBER)均(-)。荧光原位杂交检测:MYC、BCL2及BCL6均重排。诊断:伴MYC和BCL2重排弥漫性大B细胞淋巴瘤。患者未治疗,2个月后死亡。