Induction of mitotic catastrophe (MC), a tumor suppressor mechanism to maintain genomic stability, with exogenous agents is a promising therapeutic endpoint. During cell division, mitotic defects and DNA damage can lead to mitotic failure and eventual MC. Alpha-thalassemia/mental retardation syndrome X-linked (ATRX) play an important role in DNA replication and damage repair, in addition to enhancing sister chromatid cohesion to maintain mitosis. However, the effects of ATRX knockdown (KD) on irradiation-induced MC and the underlying mechanism remain unclear. Therefore, the aim of the present study was to clarify the effects and mechanisms of ATRX KD on irradiation-induced MC in p53-wild type, p53-deficient and p53-mutant cancer cells. The results showed that irradiation induced G2/M phase arrest in three cells, while ATRX KD induced additional G1 phase arrest and S phase delay in irradiated HCT116 p53+/+ cells. Notably, ATRX KD induced typical characteristics of MC exclusively in p53-deficient (HCT116 p53-/-) and p53-mutant (MDA-MB-231) cells but not in p53-proficient HCT116 counterparts. This effect was mechanistically linked to the downregulation of spindle assembly checkpoint (SAC) and chromosomal passenger complex (CPC) component proteins, which exacerbated irradiation-induced MC and consequently enhanced radiation-induced proliferation inhibition and apoptosis in HCT116 p53-/- cells.

Identifying novel targets for molecular radiosensitization is critical for improving the efficacy of colorectal cancer (CRC) radiotherapy. Alpha-thalassemia/mental retardation X-linked (ATRX), a member of the SWI/SNF-like chromatin remodeling protein family, functions in the maintenance of genomic integrity and the regulation of apoptosis and senescence. However, whether ATRX is directly involved in the radiosensitivity of CRC remains unclear. Our results showed that silencing ATRX increased the radiosensitivity of HCT116 CRC cells, which was further strengthened when p53 was depleted. To explore the potential mechanism, we focused on the impact of the ionizing radiation (IR)-induced DNA damage response (DDR), apoptosis, and senescence and the activation of the Daxx/MDM2/p53 pathway caused by ATRX loss. The results showed that IR induced DNA damage and G2/M arrest after depleting ATRX, especially in p53-depleted HCT116 cells, and inhibited ATM/Chk2 pathway activation, indicating that ATRX loss leads to failure of triggering the ATM/Chk2 pathway. Accordingly, ATRX loss promotes cell apoptosis and attenuates cell senescence. Interestingly, our results indicate that ATRX loss upregulates p53 function via the Daxx/MDM2 pathway to mediate radiosensitivity. Thus, ATRX may represent a novel radiosensitizing target for CRC, particularly p53-deficient CRC.

The widespread presence of methicillin-resistant Staphylococcus aureus (MRSA) severely threatens convenient therapeutic options in the postantibiotic era. The use of combinations of existing drugs at this stage may be a viable strategy for dealing with complex drug-resistant MRSA infections. An checkerboard MIC (Minimum Inhibitory Concentration) assay, growth curve assay, bactericidal test and scanning electron microscope (SEM) assays were performed to determine whether crisaborole (AN2728), a PDE4 inhibitor for treating atopic dermatitis (AD), produced bactericidal effect with different antibiotics. Here, we identified (AN2728) produced a significant synergistic bactericidal effect with erythromycin, cefuroxime and rifampicin against different bacterial strains of Staphylococcus aureus (S. aureus), especially MRSA (FIC < 0.5) (p < 0.05). Transcriptome analysis, bacterial biofilm assay and several kit assays revealed that AN2728 could also simultaneously affect the membrane and transporter capacity of MRSA. Moreover, in a mouse skin infection model of MRSA, the combination of AN2728 and erythromycin showed remarkable treatment benefits, as shown by significantly reduced bacterial loading (p < 0.05), pathological lesions of the skin and an obvious anti-inflammatory effect (p < 0.05). To our knowledge, this study is the first to establish that AN2728 can cooperate with antibiotics such as erythromycin to completely kill MRSA and that AN2728 can be used to extend the usage life of different antibiotics to address the inevitability of severe MRSA infection.

The tumor immune microenvironment (TIME) can limit the effectiveness and often leads to significant side effects of conventional cancer therapies. Consequently, there is a growing interest in identifying novel targets to enhance the efficacy of targeted cancer therapy. More research indicates that tumor-associated macrophages (TAMs), originating from peripheral blood monocytes generated from bone marrow myeloid progenitor cells, play a crucial role in the tumor microenvironment (TME) and are closely associated with resistance to traditional cancer therapies. Lipid metabolism alterations have been widely recognized as having a significant impact on tumors and their immune microenvironment. Lipids, lipid derivatives, and key substances in their metabolic pathways can influence the carcinogenesis and progression of cancer cells by modulating the phenotype, function, and activity of TAMs. Therefore, this review focuses on the reprogramming of lipid metabolism in cancer cells and their immune microenvironment, in which the TAMs are especially concentrated. Such changes impact TAMs activation and polarization, thereby affecting the tumor cell response to treatment. Furthermore, the article explores the potential of targeting the lipid metabolism of TAMs as a supplementary approach to conventional cancer therapies. It reviews and evaluates current strategies for enhancing efficacy through TAMs' lipid metabolism and proposes new lipid metabolism targets as potential synergistic options for chemo-radiotherapy and immunotherapy. These efforts aim to stimulate further research in this area.

目的:探究不同人参(Panaxginseng C.A.Meyer)制品(白参、红参、黑参)及人参浆果发酵前后对于剧烈运动小鼠疲劳缓解及氧化损伤的保护作用.方法:通过剧烈运动诱导建立雄性ICR小鼠疲劳模型,设置空白对照组、阳性对照(红景天胶囊粉末)组以及白参、红参、黑参及人参浆果发酵前后组(0.5 g/(kgmb·d)),每组12只小鼠,连续给药30d,测定小鼠体质量、摄食量以及血清中尿素氮、乳酸浓度和肌肉乳酸含量,分析小鼠血糖浓度变化,测定肌肉及肝脏中糖原含量,肝脏内谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、总超氧化物歧化酶及丙二醛(malondialdehyde,MDA)水平,分析抗疲劳指标与抗氧化指标的相关性.结果:各组小鼠的体质量随干预时间延长而增加,干预30 d后各组小鼠体质量增幅差异不明显,各组小鼠摄食量变化不明显.与阳性对照组相比,黑参发酵后能极显著延长小鼠力竭游泳时间(P＜0.01),极显著降低血清乳酸、血清尿素氮浓度及肌肉乳酸含量(P＜0.01).与空白对照组相比,阳性对照组具有较强的对疲劳应激诱导氧化损伤的防护作用.与阳性对照组比较,发酵后的黑参能够显著提高小鼠体内血糖浓度、肝糖原及肌糖原含量(P＜0.05),同时也能够极显著提高GSH-Px活力(P＜0.01),极显著降低肝脏中MDA含量(P＜0.01).结论:在同一给药剂量下,发酵后的黑参较其他参类及红景天胶囊粉末表现出更好的抗疲劳和抗氧化效果,能够减轻或消除由疲劳应激诱导的氧化损伤,保护机体免受氧化应激的侵害,起到抗运动疲劳的功效.

Radioresistance of breast cancer is a major reason for therapeutic failure and limits further increases in the dose of radiation due to severe adverse effects. Recently, long noncoding RNAs (lncRNAs) have been shown to regulate cancer proliferation, chemoresistance, and radioresistance. Among these lncRNAs, lncRNA GAS5 expression was shown to be downregulated in breast cancer and related to trastuzumab resistance. However, its role in the radiation response is unclear. In this study, we demonstrated that lncRNA GAS5 expression was reduced in irradiated cells and that overexpression of GAS5 reduced cell viability and promoted cell apoptosis after irradiation. Moreover, overexpression of GAS5 resulted in increased G2/M arrest and unrepaired DNA damage, indicating a radiosensitizing role of GAS5 in breast cancer cells. Finally, we found that a GAS5-interacting miRNA, miR-21, reversed the radiosensitizing effects of GAS5 by inhibiting the apoptotic pathway. In conclusion, we found that lncRNA GAS5 sensitized breast cancer cells to ionizing radiation by inhibiting DNA repair and suppressing miR-21, identifying novel targets for breast cancer radiosensitization.

近年来，案例式教学法（Case-based learning,CBL）广泛应用于我国高等教育的课程中并初见成效，临床医学作为以实践与经验为主的学科，具有其特殊性。我们发现案例式教学法比较适合于临床医学教育，教师通过临床典型病例，引导学生联系已知基础或临床理论知识来解决案例中的问题，虽然该模式很好的调动了学生的积极性，培养了他们的临床实践能力和学术兴趣，但其扩展性及创新性尚显不足。而循证医学作为现代医学的里程碑，

Previous studies have demonstrated that endoplasmic reticulum stress (ERS) might play a major role in inducing cellular autophagy and apoptosis in multiple types of cancer. Herein, we observed that trans-3,5,4'-trimethoxystilbene (TMS) exposure facilitated apoptotic cell death and ERS-mediated autophagy in colon cancer SW480 and HCT116 cells. Interestingly, our data demonstrated that ERS was not involved in TMS-induced apoptosis. However, ERS notably induced protective autophagy in SW480 and HCT116 cells. In addition, inhibiting cellular ERS significantly improved the pro-apoptotic effects of TMS. Thus, our results indicated that TMS-mediated autophagy was dependent on ERS, while apoptotic cell death might be induced in the ERS-independent pathway after TMS treatment. Generally, inhibiting ERS-mediated autophagy can enhance the pro-apoptotic effects of TMS. TMS might be a potential therapeutic agent for colon cancer treatment.

Autophagy plays a double-edged sword for cancer; particularly, mitophagy plays important roles in the selective degradation of damaged mitochondria. However, whether mitophagy is involved in killing effects of tumor cells by ionizing radiation (IR) and its underlying mechanism remain elusive. The purpose is to evaluate the effects of mitochondrial ROS (mROS) on autophagy after IR; furthermore, we hypothesized that KillerRed (KR) targeting mitochondria could induce mROS generation, subsequent mitochondrial depolarization, accumulation of Pink1, and recruitment of PARK2 to promote the mitophagy. Thereby, we would achieve a new strategy to enhance mROS accumulation and clarify the roles and mechanisms of radiosensitization by KR and IR. Our data demonstrated that IR might cause autophagy of both MCF-7 and HeLa cells, which is related to mitochondria and mROS, and the ROS scavenger N-acetylcysteine (NAC) could reduce the effects. Based on the theory, mitochondrial targeting vector sterile α- and HEAT/armadillo motif-containing protein 1- (Sarm1-) mtKR has been successfully constructed, and we found that ROS levels have significantly increased after light exposure. Furthermore, mitochondrial depolarization of HeLa cells was triggered, such as the decrease of Na+K+ ATPase, Ca2+Mg2+ ATPase, and mitochondrial respiratory complex I and III activities, and mitochondrial membrane potential (MMP) has significantly decreased, and voltage-dependent anion channel 1 (VDAC1) protein has significantly increased in the mitochondria. Additionally, HeLa cell proliferation was obviously inhibited, and the cell autophagic rates dramatically increased, which referred to the regulation of the Pink1/PARK2 pathway. These results indicated that mitophagy induced by mROS can initiate the sensitization of cancer cells to IR and might be regulated by the Pink1/PARK2 pathway.

[This retracts the article DOI: 10.3892/ol.2021.12526.].

珠江口盆地白云凹陷是我国现今深水油气勘探的重要地区,在其南侧的荔湾X构造的珠江组在3000～3281 m以混积岩沉积为主.以荔湾X构造内含有孔虫混积岩为研究对象,通过开展岩石学和同位素地球化学研究,确定了有孔虫宿主岩石类型以及有孔虫矿化的岩相学特征,重点探讨了有孔虫的矿化机制,并最终建立了有孔虫的矿化模式.荔湾X构造珠江组混积岩的生物碎屑以有孔虫碎屑为主,有孔虫壳由刃状、等径状方解石或铁方解石组成.有孔虫的房室可分为未充填、半充填和全充填3种类型.根据有孔虫房室充填的主要自生矿物类型、产状及相互关系,可将有孔虫矿化按其形成的先后分为黄铁矿化、铁方解石化、片钠铝石化和铁白云石化4种类型,其中黄铁矿的形成可能与有孔虫软体组织的生物降解有关,铁方解石可能与有机质热脱羧作用有关,片钠铝石和铁白云石中的"碳"有深部来源的岩浆成因CO2的贡献.

Human papillomavirus (HPV) infection is related to cancer growth of vaginal, cervical, vulva, penile, anogenital, and non-genital oropharyngeal sites. HPV, as a sexually transmitted virus, infects all sexes similarly but with more significant pathological risks in women. This accounts for high mortality due to late detection and poor prognosis. The initial development and eventual progress of this cancer type depend entirely on three main oncogenes E5, E6 and E7, constitutively expressed to lead to carcinogenesis. Despite an opportunity for pharmacological therapy, there is still a shortage of medical treatment that may remove HPV from infected lesions. This study offers a concise summary of the nature of the issue and the current status of work on potential lead molecules and therapeutic approaches that show the capacity of HPV therapies to counteract the roles of deregulation of E5, E6, and E7.

目的:探讨线粒体靶向KillerRed (mtKR)增强辐射诱导HeLa细胞线粒体失能及细胞自噬作用,并阐明其相关分子机制.方法:线粒体靶向质粒PTEN诱导激酶1(Pink1)-mtKR转染HeLa细胞后,进行可见光和4GyX射线照射,实验分为对照组、空载体组、Pink1-mtKR组、对照+4GyX射线照射组、空载体+4GyX射线照射组和Pink1-mtKR+4 Gy X射线照射组.X线照射后24 h,采用流式细胞术检测线粒体膜电位(MMP)和细胞自噬率,采用生化试剂盒检测线粒体呼吸链复合物Ⅰ和Ⅲ水平,采用Western blotting法检测自噬分子P62、Pink1、帕金蛋白(parkin)和线粒体外膜转换酶20 (Tom20)的表达量.结果:Pink1-mtKR瞬时转染HeLa细胞后,给予可见光联合4GyX射线照射,与对照组比较,Pink1-mtKR组细胞MMP、线粒体呼吸链复合物工和Ⅲ水平均明显降低(P＜0.05),细胞自噬率明显升高(P＜0.05),Pink1-mtKR+4 GyX射线照射组细胞MMP、线粒体呼吸链复合物Ⅰ和Ⅲ水平进一步降低(P＜0.05),自噬率进一步升高(P＜0.05).与对照组比较,Pink1-mtKR组和Pink1-mtKR+4 Gy X射线照射组细胞总蛋白中Pink1和parkin蛋白表达量无明显变化,而P62蛋白表达量增加,Pink1-mtKR组和Pink1-mtKR+4 Gy X射线照射组细胞线粒体蛋白中Pink1、parkin和Tom 20蛋白表达量均明显增加.结论:mtKR可增强辐射诱导的线粒体失能和自噬,其机制可能涉及到Pink1/parkin自噬通路的调控.

目的 探讨广场舞训练对老年乳腺癌患者睡眠、疲乏和生活质量的影响.方法 将2017年6月～12月间吉林大学中日联谊医院收治的完成术后放疗的老年乳腺癌患者101例,按照随机数字表法分为研究组(50例)和对照组(51例).对照组接受常规健康咨询和随访,研究组在此基础上每天接受1h的广场舞训练.在放疗结束时、放疗后6个月,采用匹兹堡睡眠质量指数(PSQI)评价睡眠质量,采用Piper疲乏修订量表(PFS-R)评价疲劳状况,采用生活质量核心调查表(QLQ-c 30)评价生活质量.结果 放疗后6个月,研究组的PSQI、PFS-R和QLQ-c30优于放疗结束时和对照组(P＜0.05);对照组PFS-R优于放疗结束时(P＜0.05).研究组的PSQI、PFS-R和QLQ-c30在放疗结束时、放疗后6个月评分差值大于对照组(P＜0.05).结论 广场舞训练可以有效改善老年乳腺癌患者睡眠质量,缓解疲乏,提高患者的生活质量.

目的 探讨辐射对沉默ATRX的肺癌H460细胞增殖和DNA损伤修复的影响及二者的关系.方法 靶向ATRX的3个慢病毒载体转染293T细胞后,慢病毒感染H460细胞,获得ATRX低/无表达的细胞株shATRX1-H460、shATRX2-H460和shATRX3-H460,并以shControl-H460作为对照,利用Western blot检测沉默效率.分别以克隆形成实验检测细胞增殖,免疫荧光技术检测γH2AX和Rad51焦点数,同时以Western blot检测PARP1、γH2AX和Rad51蛋白的表达.结果 shControl-H460细胞中可见ATRX表达,而shATRX1-H460、shATRX2-H460和shATRX3-H460细胞中ATRX表达均出现不同程度的降低.克隆形成实验显示,shATRX2-H460和shATRX3-H460细胞的存活分数(survival fraction,SF)均较shControl-H460细胞降低.shControl-H460和shATRX3-H460细胞经4Gy照射后1h,γH2AX焦点最多,而3 h时Rad51焦点最多,而后均降低,与shControl-H460细胞比较,在1和6h时shATRX3-H460细胞γH2AX焦点,以及1、3和6h时Rad51焦点显著增加(P＜0.05,P＜0.001).而且shATRX3-H460细胞中PARP1、γH2AX和Rad51蛋白在3和6h时均较shControl-H460细胞表达增加.结论 成功地获得靶向沉默ATRX的细胞模型,辐射后细胞增殖能力降低,可能与DNA损伤修复能力降低有关.

作为天然CO2的示踪矿物,片钠铝石的形成与CO2充注密切相关.莺歌海盆地乐东区乐东X构造莺歌海组-黄流组CO2气藏内发育含片钠铝石砂岩,在开展的岩石学和地球化学研究基础上,确定了研究区片钠铝石的产状和纵向分布特征,分析了形成片钠铝石的"碳来源"和气水条件,进而探讨了与片钠铝石具有成因联系的CO2的成因.乐东X构造含片钠铝石砂岩为细—极细粒长石石英砂岩和岩屑石英砂岩,片钠铝石主要以充填孔隙及交代颗粒的形式产出,是成岩共生序列中形成较晚的自生矿物之一.在纵向上,片钠铝石仅集中发育于高含CO2气层的底部以及其下的水层中,这一分布特征以地质实例的形式证实了片钠铝石的形成需要水的参与.研究区浅层CO2充注后形成的碳酸盐矿物为片钠铝石和铁白云石.片钠铝石的碳氧同位素特征表明形成片钠铝石的"碳"与LDX构造气层中CO2具有相同的碳来源,以无机幔源成因CO2为主.红河断裂以及莺歌海盆地中央坳陷内一系列底辟构造及伴生的垂向裂隙可能为CO2的运移通道.

Cancer remains to be a major challenge for public health providers, and is the second leading cause of death worldwide. Therefore, it is imperative to explore the mechanisms underlying cancer initiation and development, and design novel diagnostics and therapeutics. Circular RNAs (circRNAs), which exhibit a covalently closed loop structure, are involved in a variety of diseases, including cancer. The aberrant expression of circRNAs contributes to the initiation and development of various cancers by disrupting the interplay of specific signaling pathways, including the Wnt/β-catenin pathway, which controls a plethora of cellular processes that drive cancer development. The interactions between circRNAs (specifically expressed in different cancer tissues) and Wnt/β-catenin signaling pathway presents potential diagnostic biomarkers and novel therapeutic targets. In this review, we have summarized research discoveries on the functions of Wnt/β-catenin pathway-related circRNAs in the modulation of oncogenesis and progression of different types of cancer. We anticipate that our findings will contribute to the improvement or development of circRNAs-based strategies for cancer treatment.

Objective To investigate the effect of nutrition intake method with adaptive viscosity on nutritional status of laryngeal cancer patients with dysphagia after surgery and radiotherapy (RT).Methods 77 laryngeal carcinoma patients with dysphagia after surgery and radiotherapy were divided randomly into two groups by a random number table as study group (SG,n=39) and control group (CG,n=38).The CG received routine diet instruction and swallowing training,while the SG received oral nutritional supplementation with adaptive viscosity in additon.The body weight,body mass index (BMI),hemoglobin,albumin,prealbumin and scores of nutritional status at the end and 3 months after RT were compared between the two groups.Results There were 34 patients (87.2％) and 32 patients (84.2％) with nutritional status scores more than or equal to 2 at the end of RT in the two groups.At 3 months after RT,the body weight,BMI,hemoglobin,albumin,prealbumin,daily intake and nutritional status scores in the study group were significantly higher than those at the end of RT and those in the control group [(61.28±11.16) vs.(51.82±7.36),(56.44±10.69) kg;(20.57±6.13)vs.(18.81±4.43),(19.47±5.36) kg/m2;(134.87±17.86)vs.(114.68±15.25),(123.58±19.34) g/L;(40.74±7.54) vs.(36.77±5.27),(37.94±8.47) g/L;(312.83±35.83) vs.(271.56±32.82),(290.73±41.38) g/L;(2 047±126) vs.(1 512±143),(1 589±138) kcal;(2.36±0.93) vs.(3.70±1.80),(3.14±1.26);P all＜0.05].The level of the body weight and hemoglobin in the control group at 3 months after RT were significantly higher than those at end of RT [(56.44±10.69) vs.(51.56±8.34) kg,P=0.025;(123.58±19.34) vs.(113.36±16.56) g/L,P=0.023].During 3 months,the rate of pulmonary infection was 1 (2.5％) in the study group and 6 (15.8％) in the control group and the difference was statistically significant (x2 =4.073,P =0.044).Conclusion Nutrition intake method with adaptive viscosity can effectively improve the nutritional status of laryngeal cancer patients with dysphagia after surgery and radiotherapy and reduce the infection rate of lung.