BACKGROUND:D-ribose, a highly reducing pentose sugar, can be phosphorylated by ribokinase (RBKS) to form ribose-5-phosphate (R-5-P). Elevated urinary D-ribose levels have been reported in patients with type 2 diabetes mellitus (T2DM) and Alzheimer's disease, implicating its potential role in disease pathogenesis. Previous investigations into D-ribose cytotoxicity have primarily focused on its non-enzymatic glycation activity, while alternative mechanisms remain underexplored. Since hemoglobin is a major in vivo target of glycation, this study utilized K562 cells-which retain inducible hemoglobin expression-to explore additional cytotoxic mechanisms of D-ribose. METHODS AND RESULTS:CCK-8 assays demonstrated that D-ribose inhibited K562 cell proliferation in a concentration- and time-dependent manner, and this inhibitory effect was significantly enhanced in both hemin-induced differentiated and RBKS knockout K562 cells. Conversely, RBKS overexpression promoted proliferation and alleviated oxidative stress in K562 cells. Transcriptomic analysis revealed that differentially expressed genes in D-ribose-treated cells were enriched in mineral absorption and oxidative phosphorylation pathways (KEGG), as well as in biological processes related to copper ion homeostasis (GO). RT-qPCR confirmed that both D-ribose treatment and RBKS knockout downregulated key copper homeostasis genes (e.g., SLC31A1, MT1F, ATOX1) and mitochondrial respiratory chain genes (e.g., COX17, COX11, MTATP8, MTND6), and were accompanied by a significant reduction in intracellular free copper levels. CONCLUSIONS:These findings reveal a novel cytotoxic mechanism mediated by the RBKS-copper-oxidative phosphorylation axis in D-ribose-treated K562 cells, providing key insights into the intracellular role of D-ribose.

D-ribose, an ubiquitous pentose compound found in all living cells, serves as a vital constituent of numerous essential biomolecules, including RNA, nucleotides, and riboflavin. It plays a crucial role in various fundamental life processes. Within the cellular milieu, exogenously supplied D-ribose can undergo phosphorylation to yield ribose-5-phosphate (R-5-P). This R-5-P compound serves a dual purpose: it not only contributes to adenosine triphosphate (ATP) production through the nonoxidative phase of the pentose phosphate pathway (PPP) but also participates in nucleotide synthesis. Consequently, D-ribose is employed both as a therapeutic agent for enhancing cardiac function in heart failure patients and as a remedy for post-exercise fatigue. Nevertheless, recent clinical studies have suggested a potential link between D-ribose metabolic disturbances and type 2 diabetes mellitus (T2DM) along with its associated complications. Additionally, certain in vitro experiments have indicated that exogenous D-ribose exposure could trigger apoptosis in specific cell lines. This article comprehensively reviews the current advancements in D-ribose’s digestion, absorption, transmembrane transport, intracellular metabolic pathways, impact on cellular behaviour, and elevated levels in diabetes mellitus. It also identifies areas requiring further investigation.

Background:Pulmonary large-cell neuroendocrine carcinoma (PLCNEC) is a rare and highly malignant lung cancer. Due to the paucity of data from clinical studies, its clinical characteristics and treatment remain controversial. The present study explored factors influencing the prognosis and survival outcomes of patients with PLCNEC and developed a dependable prognostic model using machine learning. Methods:The clinical data of PLCNEC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2020. A total of 2,897 PLCNEC patients were enrolled and univariate and multivariate Cox regression analyses were performed to explore independent prognostic factors for disease-specific survival (DSS). Ten machine learning algorithms were utilized to predict the 2-year survival. The clinicopathological data collected from The First Affiliated Hospital of Sun Yat-sen University between 2010 and 2022 were used to test the trained machine. Results:Sex [hazard ratio (HR) 1.168, 95% confidence interval (CI): 1.063-1.284], age (HR 1.262, 95% CI: 1.144-1.391), surgery (HR 0.481, 95% CI: 0.413-0.559), chemotherapy (HR 0.450, 95% CI: 0.404-0.501), bone metastasis (HR 1.284, 95% CI: 1.124-1.466), brain metastasis (HR 1.167, 95% CI: 1.023-1.331), liver metastasis (HR 1.223, 95% CI: 1.069-1.399), American Joint Committee on Cancer-Node (AJCC-N), and tumor stage were independent prognostic factors. The gradient boosting decision tree (GBDT) performed better than other models, with an F1-score of 0.791 and an area under the curve of 0.831. Conclusions:Male, age ≥65 years, distant metastasis to the bone, liver, and brain are associated with a worse prognosis in PLCNEC patients, while surgery and chemotherapy are associated with improved prognosis. GBDT showed promising performance in predicting 2-year survival, which can serve as a valuable reference for clinical diagnosis and treatment of PLCNEC.

Background: Increasing evidence indicates that four and a half LIM domains 2 (FHL2) plays a crucial role in the progression of various cancers. However, the biological functions and molecular mechanism of FHL2 in lung adenocarcinoma (LUAD) remain unclear. Methods: We evaluated the prognostic value of FHL2 in LUAD using public datasets and further confirmed its prognostic value with our clinical data. The biological functions of FHL2 in LUAD were evaluated by in vitro and in vivo experiments. Pathway analysis and rescue experiments were subsequently performed to explore the molecular mechanism by which FHL2 promoted the progression of LUAD. Results: FHL2 was upregulated in LUAD tissues compared to adjacent normal lung tissues, and FHL2 overexpression was correlated with unfavorable outcomes in patients with LUAD. FHL2 knockdown significantly suppressed the proliferation, migration and invasion of LUAD cells, while FHL2 overexpression had the opposite effect. Mechanistically, FHL2 upregulated the PI3K/AKT/mTOR pathway and subsequently inhibited autophagy in LUAD cells. The effects FHL2 on the proliferation, migration and invasion of LUAD cells are dependent on the inhibition of autophagy, as of induction autophagy attenuated the aggressive phenotype induced by FHL2 overexpression. Conclusions: FHL2 promotes the progression of LUAD by activating the PI3K/AKT/mTOR pathway and subsequently inhibiting autophagy, which can be exploited as a potential therapeutic target for LUAD.

成熟红细胞(erythrocyte)由于无细胞核及含膜细胞器,主要通过糖酵解和磷酸戊糖途径进行能量代谢.糖酵解产生的三磷酸腺苷(adenosine triphos-phate, ATP)作为红细胞内主要能源物质,以往认为主要用于维持红细胞正常功能.早在1997年Mc-Cullough等就观察到缺氧或红细胞变形时,ATP可以被红细胞释放到细胞外,通过血管平滑肌细胞(vas-cular smooth muscle cells, VSMC)和内皮细胞(endo-thelial, EC)合成并释放一氧化氮(nitric oxide, NO)影响微循环,且红细胞释放ATP的改变可能与某些疾病发生发展存在联系[1].本文从红细胞内ATP释放机制、效应及与疾病关系等方面进行综述,以期为后续红细胞能量代谢研究提供参考.

新时代高校教学要以立德树人为根本,努力将思政内容有机融入各门课程的教学.机能实验学作为融生理学、药理学和病理生理学为一体的综合性实验课程,是医学生必修的主干课程.课程组以"目标—案例—方法"为主线,针对不同的实验内容设计相应的思政教育主题,使课程在贴合实际的同时,又具有教育意义.这为今后机能实验学的课程体系发展开创了全新的思路,对学生核心价值观的培养也具有重要意义,从而切实提高机能实验学的教学效果和育人水平.

生物化学与分子生物学实验技术是包头医学院医学专业必修基础课,也是生物医学的前沿学科,对培养卓越医学生科技创新能力非常重要.为了使学生获得最优学习效果,2016年,我们将优慕课、雨课堂及虚拟仿真实验平台等信息化工具应用到教学活动中,开展了线上与线下有机结合的混合式教学,6年的实践结果表明:混合式教学提高了学生的参与度,激发了学生对生物化学与分子生物学实验技术的学习兴趣,改善了学习态度,增强了学生发现问题、分析问题、解决问题的能力和创新能力.

d-Ribose is not only an important component of some biomacromolecules, but also an active pentose with strong reducibility and non-enzymatic glycation ability. Previous studies reported the diverse role of d-ribose in different cells. In this study, the effects of d-ribose on non-enzymatic glycation of hemoglobin (Hb), as well as eryptosis, oxidative stress and energy metabolism of erythrocytes were observed by molecular fluorescence spectrophotometry, multi-wavelength spectrophotometry, high-pressure liquid chromatography (HPLC), mass spectrometry (MS) and flow cytometer. The results showed that d-ribose had the strongest non-enzymatic glycation ability to Hb in vitro when compared with other monosaccharides, and could enter the erythrocytes in a concentration-dependent manner, which was not inhibited by the specific glucose transporter 1 (GLUT1) inhibitor WZB117. In addition, d-ribose incubation increased the HbA1c, hemolysis, eryptosis, and ROS level of erythrocytes significantly more than that of d-glucose, however, no changes were observed in the levels of ATP, NADPH, and other intermediate energy metabolites in d-ribose treatment. Therefore, the strong non-enzymatic glycation ability of d-ribose may play an important role in erythrocyte damage.

Objective To explore the effect of melatonin on the storage damage of red blood cells（RBCs） from the aspects of oxygen-carrying function and oxidative stress response.Methods The blood of 5 healthy volunteer blood donors were taken, RBCs were suspended in 100 ml of RBCs maintenance solution and divided into control group（physiological saline solution with 0.01% absolute ethanol） and melatonin group（melatonin 1 μg/ml）. The cells of each group were gently mixed in a blood bag and stored in a refrigerator at 2～6℃ for 1, 7, 14, 28, 35, 42 d respectively. 5 ml of blood was taken to prepare a blood smear, and RBCs morphology was detected with Wright staining method; the levels of hemolysis indicators sodium ion（Na + ）, potassium ion（K + ）, and free hemoglobin（FHb） were detected; the oxygen affinity（P50）, 2,3-diphosphoglycerate（2,3-DPG） and Na + -K + -ATPase were detected, and the oxygen carrying capacity of RBCs was comprehensively evaluated. The levels of high iron hemoglobin（MetHb）, malondialdehyde（MDA）, superoxide dismutase（SOD）, thioredoxin peroxidase（Prx）2, total antioxidant capacity（T-AOC） in RBCs were detected with spectrophotometry, and the level of oxidative stress was evaluated. Results With the prolongation of storage time, the spinous and spherical changes of RBCs increased in the control group, the levels of FHb, Na + ,MetHb and MDA were gradually increased, the levels of K + ,P50, 2,3-DPG, Na + -K + -ATPase, SOD, Prx2 and T-AOC were gradually decreased.After adding melatonin to the storage solution, compared with the control group, the number of deformed cells and the levels of FHb, Na + ,MetHb and MDA were gradually decreased in melatonin group（P＜0.05）, the levels of K + ,P50, 2,3-DPG, Na + -K + -ATPase, SOD, Prx2 and T-AOC were gradually increased in melatonin group（P＜0.05）.Conclusions Melatonin could improve the oxygen-carrying function and oxidative stress level of RBCs during storage, and prolong the storage time of RBCs.

Lung cancer is the primary cause of cancer-related mortality worldwide. Hemoglobin (Hb) represents the most widely utilized test parameter in clinical settings. However, few articles have examined the causal relationship between Hb concentration and lung cancer incidence. Mendelian randomization (MR) was first conducted to investigate the potential causality between Hb and lung cancer. Sensitivity analyses were applied to validate the reliability of MR results. Then, the National Health and Nutrition Examination Survey (NHANES) database was used to verify the effect of Hb on the prognosis of lung cancer. The MR analysis demonstrated that Hb was casually associated with the decreased risk of lung cancer in the European population (ORIVW 0.84, 95

本文以医学微生物学第二十五章"冠状病毒"为例,以"问题驱动"为主线,灵活选择和采用与教学策略相适应的信息技术工具,搭建超越时空和地域限制的"空中课堂",培养医学生"立德树人"与提升专业素养无缝衔接.期望本教学案例为进一步推动医学院校教师信息技术应用能力的提高、提升医学生人文素养,提供借鉴和参考.

Introduction . Oxidative stress is one of the important causes of red blood cells (RBCs) storage lesion. As a hormone, melatonin (MT) is also an effective antioxidant, however the pro- and antioxidative properties of MT depend on the cell type, redox state, as well as experimental conditions. Aim of this study — to investigate the protective effects of low concentration of MT on the stored RBCs in vitro . Materials and methods . Leukofi ltered RBCs were incubated in MAP RBC additive solution with or without 150 pg/mL of MT for 42 days under blood bank conditions. The morphology, aggregation index, methemoglobin (MetHb), m alondialdehyde (MDA), glucose, lactic acid and ATP of RBCs were detected on days 0, 7, 14, 21, 28, 35 and 42 to observe the protective effects of MT during the storage of RBCs. Results . During RBCs s torage, the number of deformed RBCs, relative hemolysis rate, aggregation index, MDA and MetHb were signifi cantly affected by both storage time (p < 0.0001) and melatonin (p < 0.01), and they had interaction only on the number of deformed RBCs (p < 0.0001). The concentration of glucose, lactic acid and ATP were affected by storage time (p < 0.0001), but not by MT concentration (p > 0.05). The number of deformed RBCs, relative hemolysis rate, MDA and MetHb in MT group were signifi cantly lower than that in control group at the end of storage stage (p < 0.05). Conclusion . Our study showed low hypnotic drug concentration of MT is speculated to have protective effects on the quality of stored RBCs through antioxidative mechanism.

通过教学改革和实践建立以立德树人为目标的生物化学与分子生物学一流本科课程,主要面向2017级—2020级的临床、法医、麻醉、预防等专业五年制医学本科生实施多维度的混合式教学,包括:结合网络教学平台、结合雨课堂、结合"翻转课堂"、结合第二课堂、结合形成性评价的混合式教学.网络教学平台包含丰富的资源,教学过程分课前、课中和课后3个阶段,实现课程思政的有机融入.整个教学过程真正实现课堂教学和线上学习的有机结合,使学生充分利用碎片时间进行学习,引导学生发现问题、思考问题和解决问题,培养学生的自主学习能力.通过成绩分析和问卷调查显示混合式教学效果良好.

目的:研究体外存储对红细胞衰亡(eryptosis)的影响.方法:募集6名健康成年志愿献血者,分别采集400 mL抗凝全血,滤白后离心去除血浆,将红细胞(red blood cells,RBC)重悬于100 mL MAP红细胞保护液中,4℃保存.于储存期0、7、14、21、28和35 d分别抽取血样6 mL,利用流式细胞仪、全自动血细胞计数仪、血气分析仪等分别检测RBC膜磷脂酰丝氨酸(phosphatidylserine,PS)含量、红细胞平均体积(mean corpuscular volume,MCV)、细胞外离子浓度、细胞外葡萄糖(glucose,Glu)、乳酸(lactic acid,Lac)、总胆红素(total bilirubin,TBil)浓度及高铁血红蛋白分数(fraction of methemoglobin,FMetHb).结果:随着存储时间延长,PS含量降低(r=-0.8356),MCV、细胞外Cl-浓度没有变化,细胞外TBil浓度(r=0.8035)、Lac浓度(r=0.9377)及FMetHb(r=0.9706)随存储时间延长不断增加,细胞内Na+浓度(r=-0.9274)和Glu浓度(r=-0.9860)随存储时间延长降低.结论:体外存储并不引起RBC衰亡增加.

红细胞结构和组成的特殊性使其更容易受到自由基的攻击而发生氧化损伤.除了红细胞内强大的抗氧化酶外,维生素C是红细胞内重要的非酶抗氧化物质.从食物中消化吸收的维生素C在血液中首先转变为脱氢抗坏血酸(dehydroascorbic acid,DHA),然后与葡萄糖共用红细胞膜葡萄糖转运蛋白1(glucose transporter-1,GLUT-1)而被转运入红细胞,在胞内DHA再被还原为维生素C发挥抗氧化损伤的作用.因此,研究红细胞膜GLUT-1对DHA与葡萄糖转运的精细调节,可以为糖尿病等相关疾病的预防、诊断和治疗提供新的思路.

Objective To investigate the relationship between erythrocyte (RBC) deformability and RBC energy metabolism in patients with type 2 diabetes mellitus (T2DM). Methods Totally 80 T2DM and 50 controls with age of 40 to 70 years were selected. Rough hematology laboratory test, ATP content, Hexokinase (HK) and Pyruvate kinase (PK) activity were detected.Results BMI, DBP and SBP of patients with T2DM were higher than those of control group (P＜0.05). T2DM of RBC deformation index (TK), rigidity index(IR), RBC distribution width (RDW) and average RBC volume (MCV) were higher than that of control group (P＜0.05); The content of ATP and PK activity in RBC of T2DM group were higher than that of control group (P＜0.05), while the activity of HK was lower than that of control group(P＜0.05). In the T2DM, TK was negatively correlated with ATP content and HK activity, and positively correlated with HbA1c. IR was negatively correlated with HK and PK values, and positively correlated with HbA1c (P＜0.05). Compared with Group A, the TK value of Group C increased (P＜0.05) in the HbA1c group. Compared with Group A, Group C had higher ATP, PK and HK (P＜0.05). Compared with Group A, ROS in Group C increased (P＜0.05). Results RCD damage in diabetic patients is closely related to HbA1c, and RBC energy metabolism plays an important role in maintaining RCD. In diabetic patients, ATP production in RBC increased, PK activity increased, and energy metabolism was vigorous, but this did not improve the reduced RCD status caused by high glucose. Conclusions The energy metabolism of erythrocytes in diabetic patients was more vigorous and is closely related to the decrease of RCD. RCD reduction is a risk factor for diabetic microangiopathy, so monitoring erythrocytes energy metabolism may provide a new basis for monitoring the progress of clinical diabetes patients and support clinical diagnosis and treatment.