作者机构：
[He, Bisha; Hu, Yibao; Cao, Qian; Li, Yue; Tang, Yun; Cao, Ting; Zhou, Xiangping] Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan 421001,China;[Liu, Shuangquan] Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan 421001,China. Electronic address: dantelliu@163.com
通讯机构：
[Liu, Shuangquan] D;Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan 421001,China. Electronic address:
关键词：
Angiogenesis;Ferroptosis;Molecular mechanism;Unfolded protein response
摘要：
Angiogenesis is the growth of new blood vessels on preexisting ones. It is the outcome of a multifactorial effect involving several cells, which can be brought on by different stress reactions.The accumulation of unfolded proteins in the endoplasmic reticulum occurs when cells are stressed due to environmental changes, where physical or chemical stimuli induce endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR), a homeostasis response designed to re-establish protein balance. Ferroptosis is a planned death of lipid peroxidation and anomalies in metabolism that is dependent on iron. Large concentrations of iron ions accumulate there, along with high concentrations of lipid peroxides and reactive oxygen species, all of which can contribute to the development of several diseases. Through the production of growth factors, adhesion factors, and inflammatory factors that trigger the start of angiogenesis, both UPR and Ferroptosis can be implicated in angiogenesis.To set the stage for further research on angiogenesis, this work concentrated on the effects of Ferroptosis and UPR on angiogenesis, respectively.
期刊：
Journal of Translational Medicine,2024年22(1):1-11 ISSN：1479-5876
作者机构：
[Wu, Ling; Ouyang, Qianhui; Huang, Xiangping; Hong, Lanhui] Department of Clinical Laboratory, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), 61 Jiefang Road, Changsha, 410005, Hunan, People's Republic of China;[Liu, Sixiang; Huang, Ying] Department of Emergency, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha, Hunan, China;[Yang, Kongzhi; Ning, Ding] Department of Emergency Medical, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China;[Tan, Chao Chao] Tumor Immunity Research Center of Hunan Provincial Geriatric Institute (Hunan Provincial People's Hospital), Changsha, Hunan, China. tchchwolf@163.com;[Tan, Chao Chao] Department of Clinical Laboratory, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China. tchchwolf@163.com
关键词：
Acute pancreatitis;Infected pancreatic necrosis;Neutrophil CD64 index
摘要：
OBJECTIVE: Infectious pancreatic necrosis (IPN) is a serious complication of acute pancreatitis, and early recognition and timely intervention are the keys to improving clinical outcomes. The purpose of this study was to investigate the predictive capacity of the neutrophil CD64 index (nCD64 index) on IPN in patients with acute pancreatitis METHODS: This study comprises two independent cohorts: the training cohort consisted of 202 patients from Hunan Provincial People's Hospital, and the validation cohort consisted of 100 patients from Changsha Central Hospital. Peripheral blood samples were collected on the day of admission and on the 3rd, 5th, 7th, and 10th days of hospitalization, and the nCD64 index was detected by flow cytometry. Additionally, relevant clinical characteristics and laboratory biomarkers were collected and analyzed. RESULTS: We observed that nCD64 index on admission was significantly higher in the IPN group than Non-IPN group (p < 0.001). In the training cohort, a higher occurrence rate of IPN was observed in the high nCD64 index group compared to the moderate and low nCD64 index group (p < 0.001). Further analysis showed that nCD64 index was significant positive correlated with the incidence rate of IPN (p < 0.001, correlation coefficient = 0.972). Furthermore, logistic regression analysis showed that high expression of the nCD64 index on admission was a risk factor for the occurrence of IPN (OR = 2.971, p = 0.038). We further found that the nCD64 index of IPN patients was significantly higher than the Non-IPN patients on the days 1, 3, and 5 after admission, and the nCD64 index of IPN patients before and after the onset (p < 0.05). At the same time, this study revealed that the nCD64 index on admission showed good predictive efficacy for IPN (AUC = 0.859, sensitivity = 80.8%, specificity = 87.5%), which was comparable to APACHE II score. And this finding was further validated in an independent cohort of 100 participants (AUC = 0.919, Sensitivity = 100.0%, Specificity = 76.6%). CONCLUSION: This study demonstrated the clinical value of nCD64 index in patients with IPN patients for the first time through two independent cohort studies. The nCD64 index can be used as an early prediction and risk assessment tool for the occurrence of IPN, contributing to the improvement of patient outcomes and efficiency of medical resource allocation.
作者机构：
[Gong, Junyi; Hou, Jie] Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421001, Peoples R China.
通讯机构：
[Hou, J ] U;Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421001, Peoples R China.
摘要：
Proton-conducting solid oxide fuel cells (H-SOFCs) are expected to be an ideal energy conversion device operating below 600 °C. However, the lack of robust electrodes with high catalytic activity remains a major obstacle to commercialization. Herein, B-site high-entropy modification is first performed on K2NiF4-type oxide to obtain a novel cathode material, La1.2Sr0.8Mn0.2Fe0.2Co0.2Ni0.2Cu0.2O4+δ (LSMFCNC). By harnessing the unique properties of multiple elements, the B-site transition metals in LSMFCNC evolve into various compound states, resulting in crystal structure expansion and a decrease in the bond strength between cations and oxygen ions, thereby promoting the formation of oxygen vacancies and achieving high proton/oxygen diffusion rates with excellent oxygen reduction reaction (ORR) activity. Ultimately, H-SOFCs using the high-entropy LSMFCNC cathode demonstrate an excellent cell performance with power outputs of 1759 mW/cm2 at 700 °C and 1126 mW/cm2 at 600 °C. This performance is superior to La1.2Sr0.8NiO4 (LSNO) and other K2NiF4-type cathodes reported in the literature. The outstanding electrochemical performance and fine operational stability suggest that LSMFCNC could be a potential cathode alternative for low-temperature H-SOFC operation. This study provides a new approach to developing highly active and durable cathodes for H-SOFCs.
摘要：
Theoretical investigations are conducted to examine the impact of toroidal rotation and ion collisional viscosity on low-frequency zonal flow (LFZF) in a tokamak plasma with the fluid model. The results indicate that while the frequency of LFZF remains unchanged during an isothermal process with gamma=1, its damping rate is influenced by both toroidal rotation and ion collisional viscosity. Specifically, as the ion collisional viscosity increases, so does the damping rate of LFZF; conversely, as the toroidal rotation As its Mach number rises, its damping rate decreases. For a non-isothermal process with gamma > 1 (such as gamma = 5/3), the damping rate and frequency of LFZF are influenced by both toroidal rotation and ion collisional viscosity. It has been demonstrated that when the toroidal rotation Mach number surpasses a certain threshold, the frequency transitions from zero to a finite value, while the damping rate decreases as the toroidal rotation Mach number increases for LFZF. Furthermore, it has been observed that the damping rate of LFZF increases while the frequency decreases with an increase in ion collisional viscosity. Moreover, when the ion collisional viscosity surpasses a certain threshold, the frequency of LFZF drops to zero.
摘要：
One of the key features of cancer is energy metabolic reprogramming which is tightly related to cancer proliferation, invasion, metastasis, and chemotherapy resistance. NcRNAs are a class of RNAs having no protein-coding potential and mainly include microRNAs, lncRNAs and circRNAs. Accumulated evidence has suggested that ncRNAs play an essential role in regulating cancer metabolic reprogramming, and the altered metabolic networks mediated by ncRNAs primarily drive carcinogenesis by regulating the expression of metabolic enzymes and transporter proteins. Importantly, accumulated research has revealed that dysregulated ncRNAs mediate metabolic reprogramming contributing to the generation of therapeutic tolerance. Elucidating the molecular mechanism of ncRNAs in cancer metabolic reprogramming can provide promising metabolism-related therapeutic targets for treatment as well as overcome therapeutic tolerance. In conclusion, this review updates the latest molecular mechanisms of ncRNAs related to cancer metabolic reprogramming.
作者机构：
[Wang, YB; Wang, Youbin; Li, Yongkun; Zhou, Jiashun; Zhou, Bingtao] Guangxi Univ, Sch Resources Environm & Mat, State Key Lab Featured Met Mat & Life Cycle Safety, Nanning 530004, Peoples R China.;[Wang, YB; Wang, Youbin; He, Kezhun] Guangxi Alnan Inst Aerosp Transit Aluminum Alloy &, Nanning 530031, Peoples R China.;[Wei, Yuezhou] Univ South China, Sch Nucl Sci & Technol, Hengyang 421001, Peoples R China.
通讯机构：
[Wang, YB ] G;Guangxi Univ, Sch Resources Environm & Mat, State Key Lab Featured Met Mat & Life Cycle Safety, Nanning 530004, Peoples R China.;Guangxi Alnan Inst Aerosp Transit Aluminum Alloy &, Nanning 530031, Peoples R China.
摘要：
In order to enhance the corrosion resistance of 6061 Al, a simple and efficient electrodeposition method for one-step preparation of ZnAlCe layered double hydroxides (LDH) protective film was proposed. The microstructure and corrosion resistance of LDH film were characterized. The results indicated that the presence of Ce promoted the growth of LDH, resulting in denser, thicker ZnAlCe-LDH film, which effectively slowed down the corrosion rate of 6061Al. Particularly, the electrodeposition behavior was investigated in situ using electrochemical quartz crystal microbalance. The electrodeposition of LDH films was divided into rapid deposition of hydroxide and nucleation growth of LDH, and these two processes were described in detail. This work provided novel ideas for the preparation of LDH films on Al alloys.
作者机构：
[Xu, Changjin; Xu, CJ] Guizhou Univ Finance & Econ, Guizhou Key Lab Econ Syst Simulat, Guiyang 550004, Peoples R China.;[Liu, Zixin; Pang, Yicheng] Guizhou Univ Finance & Econ, Sch Math & Stat, Guiyang 550025, Peoples R China.;[Shen, Jianwei] North China Univ Water Resources & Elect Power, Sch Math & Stat, Zhengzhou 450046, Peoples R China.;[Liao, Maoxin] Univ South China, Sch Math & Phys, Hengyang 421001, Peoples R China.;[Li, Peiluan] Henan Univ Sci & Technol, Sch Math & Stat, Luoyang 471023, Peoples R China.
通讯机构：
[Xu, CJ ] G;Guizhou Univ Finance & Econ, Guizhou Key Lab Econ Syst Simulat, Guiyang 550004, Peoples R China.
关键词：
ergodic theory;markov Process;hessian matrix;Ito formula
摘要：
In the literature [16], the COVID-19 model has been constructed using deterministic approach. The present manuscript examines a stochastic model designed to capture the interplay between COVID-19 and varying infection rates on disease dynamics. We present the necessary criteria for a global solution to the considered model to exist and be unique. To illustrate several outcomes pertaining to the ergodic properties of the given system, the we utilize nonlinear analysis. Furthermore, the model undergoes simulation and is compared with deterministic dynamics. To verify the efficacy of the considered model and demonstrate its utility, we compare the dynamics of the infected population to real statistical data from multiple countries, such as the United Kingdom, Australia, Spain, and India. The proposed model has proven to be a reliable and effective tool for understanding the intricate nature of COVID-19 dynamics. Moreover, we provide a visually striking depiction of the impact of different infection rates on the propagation of the model under investigation. This visualization provides valuable insight into the multifaceted nature of the pandemic and significantly contributes to the comprehension of COVID-19 dynamics.
期刊：
JOURNAL OF MEDICINAL CHEMISTRY,2024年 ISSN：0022-2623
作者机构：
[Yang, Ruige; Guo, Yong; Xu, Ting] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China;[Yang, Ruige; Kang, Ayue; Yan, Xiaoting; Yang, Longhua; Guo, Yong; Tian, Yue; Qin, Shangshang; Li, Xinhui] School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
摘要：
The escalation of multidrug-resistant bacterial infections, especially infections caused by methicillin-resistant Staphylococcus aureus (MRSA), underscores the urgent need for novel antimicrobial drugs. Here, we synthesized a series of amphiphilic 2-phenyl-1H-phenanthro[9,10-d]imidazole-antimicrobial peptide (AMP) mimic conjugates (III1-30). Among them, compound III13 exhibited excellent antibacterial activity against G+ bacteria and clinical MRSA isolates (MIC = 0.5-2 μg/mL), high membrane selectivity, and low toxicity. Additionally, compared with traditional clinical antibiotics, III13 demonstrated rapid bactericidal efficacy and was less susceptible to causing bacterial resistance. Mechanistic studies revealed that III13 targets phosphatidylglycerol (PG) on bacterial membranes to disrupt membrane integrity, leading to an increase in intracellular ROS and leakage of proteins and DNA, ultimately causing bacterial cell death. Furthermore, III13 possessed good fluorescence properties with potential for further dynamic monitoring of the antimicrobial process. Notably, III13 showed better in vivo efficacy against MRSA compared to vancomycin, suggesting its potential as a promising candidate for anti-MRSA medication.
作者机构：
[Jun Li] , 栖霞区元化路6-10号中国科学院紫金山天文台, Nanjing, 210000, CHINA;[Xiao-Jun 毕效军 Bi#&#&#Jun Li] 粒子天体中心, 中国科学院高能物理研究所, 北京918信箱粒子天体中心, Beijing, 100049, CHINA;[Lin-Qing Gao] , School of Nuclear Science and Technology, University of South China, Hengyang 421001, China, Hengyang, 421001, CHINA;[Xiaoyuan Huang] , Key Laboratory of Dark Matter and Space Astronomy, Purple Mountain Observatory, Chinese Academy of Sciences, 210033 Nanjing, Jiangsu, China, Nanjing, 210033, CHINA;[Run-Min Yao] , Key Laboratory of Particle Astrophysics, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China, Beijing, 100049, CHINA
摘要：
High-energy photons may oscillate with axion-like particles (ALPs) when they propagate through the Milky Way's magnetic field, resulting in an alteration in the observed photon energy spectrum. The ultra-high energy gamma-ray spectra, measured by the Large High Altitude Air Shower Observatory (LHAASO) up to $\mathcal{O}(1)~\mathrm{PeV}$, provide a promising opportunity to investigate the ALP-photon oscillation effect. In this study, we utilize the gamma-ray spectra of four Galactic sources measured by LHAASO, including the Crab Nebula, LHAASO J2226+6057, LHAASO J1908+0621, and LHAASO J1825-1326, to explore this effect. We employ the $\rm CL_s$ method to set constraints on the ALP parameters. Combing the observations of the four sources, our analysis reveals that the ALP-photon coupling $g_{a\gamma}$ is constrained to be smaller than $1.4\times10^{-10}$ ${\rm GeV}^{-1}$ for the ALP mass of $\sim 4\times10^{-7} ~\mathrm{eV}$ at the 95\% C.L. By combing the observations of the Crab Nebula from LHAASO and other experiments, we find that the ALP-photon coupling could be set to be about $7.5\times10^{-11}$ ${\rm GeV}^{-1}$ for the ALP mass $\sim 4 \times10^{-7}~\mathrm{eV}$ , which is in close proximity to the CAST constraint.
作者机构：
[Wu, Jun-Fang; Yuan, Mei; Hu, Yan-Hong; Su, Ting; Wu, Lin] Department of Neurology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China;[Zhu, Ling-Qiang; Liu, Dan] Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
摘要：
Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by progressive degeneration of brain function. AD gradually affects the parts of the brain that control thoughts, language, behavior and mental function, severely impacting a person's ability to carry out daily activities and ultimately leading to death. The accumulation of extracellular amyloid-β peptide (Aβ) and the aggregation of intracellular hyperphosphorylated tau are the two key pathological hallmarks of AD. AD is a complex condition that involves both non-genetic risk factors (35%) and genetic risk factors (58-79%). The glymphatic system plays an essential role in clearing metabolic waste, transporting tissue fluid, and participating in the immune response. Both non-genetic and genetic risk factors affect the glymphatic system to varying degrees. The main purpose of this review is to summarize the underlying mechanisms involved in the deregulation of the glymphatic system during the progression of AD, especially concerning the diverse contributions of non-genetic and genetic risk factors. In the future, new targets and interventions that modulate these interrelated mechanisms will be beneficial for the prevention and treatment of AD.
作者机构：
[Xun Chen] School of Nuclear Science and Technology, University of South China, Hengyang 421001, China;[Mei Huang] School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 100049, China
通讯机构：
[Mei Huang] S;School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 100049, China
摘要：
Based on lattice QCD results of equation of state and baryon number susceptibility at zero baryon chemical potential, and supplemented by machine learning techniques, we construct the analytic form of the holographic black hole metric in the Einstein-Maxwell-Dilaton framework for pure gluon, 2-flavor, and ( 2+1 )-flavor systems, respectively. The dilaton potentials solved from Einstein equations are in good agreement with the extended nonconformal DeWolfe-Gubser-Rosen type dilaton potentials fixed by lattice QCD equation of state, which indicates the robustness of the Einstein-Maxwell-Dilaton framework. The predicted critical end point in the ( 2+1 )-flavor system is located at ( Tc=0.094 GeV , μBc=0.74 GeV ), which is close to the results from the realistic Polyakov-Nambu-Jona-Lasinio model, the functional renormalization group, and the holographic model with extended DeWolfe-Gubser-Rosen dilaton potential.
作者机构：
[Yu, Miao; Guo, Xin; Zhang, Kai] Sichuan Univ, Sch Mech Engn, Chengdu 610065, Peoples R China.;[Yu, Miao; Guo, Xin; Zhang, Kai] Sichuan Univ, Yibin Ind Technol Res Inst, Yibin 644000, Peoples R China.;[Kang, Xiaomin] Univ South China, Sch Mech Engn, Hengyang 421001, Peoples R China.;[Zhang, Song] Moutai Inst, Dept Food Sci & Engn, Renhuai 564502, Guizhou, Peoples R China.;[Qian, Lu; Qian, L] South China Univ Technol, Sch Mat Sci & Engn, Guangzhou 510641, Peoples R China.
通讯机构：
[Zhang, S ] M;[Qian, L ] S;Moutai Inst, Dept Food Sci & Engn, Renhuai 564502, Guizhou, Peoples R China.;South China Univ Technol, Sch Mat Sci & Engn, Guangzhou 510641, Peoples R China.
摘要：
Hyaluronic acid (HA), a vital glycosaminoglycan in living organisms, possesses remarkable mechanical and viscoelastic properties that have garnered significant attention in therapeutic, biomedical, and cosmetic applications. However, a comprehensive picture of the physicochemical and biocharacterization of HA at the single-molecule level remains elusive. In this work, atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and molecular dynamics (MD) simulation were used to investigate the nanomechanics and water retention properties of HA at the single-molecule level. The present study aims to unravel the intricate details of the influence of molecular structure on HA behavior and shed light on its unique attributes. According to the force measurements, the energy used to stretch a HA chain in water is 8.45 kJ/mol, significantly surpassing that of Curdlan (3.45 kJ/mol) and chitin (2.23 kJ/mol), both of which possess molecular structures partially similar to that of HA. Intriguingly, the strength of the intrachain interaction of HA (5.54 kJ/mol) was considerably weaker compared to Curdlan (11.06 kJ/mol) and chitin (or cellulose, 10.76 kJ/mol). This result indicates that HA exhibits a preference for interacting with water rather than with itself, thereby showing enhanced water affinity. Moreover, the force measurements demonstrated that changing the glycosidic bond from β-(1-3) (Curdlan) or β-(1-4) (chitin or cellulose) to β-(1-3) + β-(1-4) (HA) resulted in polysaccharides displaying improved water affinity and more extended conformation. These conclusions were further verified by molecular dynamics (MD) simulations. Overall, our work sheds new light on the nanomechanics and water retention properties of HA at the single-molecule level, offering valuable insights for future research in this field.
作者机构：
[Wei, Rui; Liu, Qingqing; Luo, Jun-Li; Wei, R; Sun, Yangqing; Luo, JL] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Peoples R China.;[Zhong, Shangwei; Luo, Jun-Li; Luo, JL] Univ South China, Affiliated Hosp 2, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Luo, Jun-Li; Luo, JL] Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha 410008, Peoples R China.
通讯机构：
[Wei, R; Luo, JL ] C;Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Peoples R China.;Univ South China, Affiliated Hosp 2, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha 410008, Peoples R China.
关键词：
FTSJ1;tumor promotor;CD8+T cell infiltration;triple-negative breast cancer
摘要：
Simple Summary In this study, we found that high FTSJ1 expression in triple-negative breast cancer patients was associated with poor prognosis and was associated with reduced infiltration of CD8+T cells in the tumor microenvironment. By knocking down FTSJ1, we observed an inhibitory effect on the proliferation and migration of triple-negative breast cancer, while inducing apoptosis and increasing the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. This finding highlights the importance of FTSJ1 as a potential immunotherapy target in triple-negative breast cancer.Abstract FtsJ RNA 2 '-O-methyltransferase 1 (FTSJ1) is a member of the methyltransferase superfamily and is involved in the processing and modification of ribosomal RNA. We herein demonstrate that FTSJ1 favors TNBC progression. The knockdown of FTSJ1 inhibits TNBC cell proliferation and development, induces apoptosis of cancer cells, and increases the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. Furthermore, the high expression of FTSJ1 in TNBC attenuates CD8+T cell infiltration in the tumor microenvironment (TME) correlated with poorer prognosis for clinical TNBC patients. In this study, we establish that FTSJ1 acts as a tumor promotor, is involved in cancer immune evasion, and may serve as a potential immunotherapy target in TNBC.
摘要：
OBJECTIVE: How different surgical procedures, including the robotic-assisted liver resection (RLR) and laparoscopic liver resection (LLR), can affect the prognosis of patients with liver malignancies is unclear. Thus, in this study, we compared the effects of RLR and LLR on the surgical and oncological outcomes in patients with liver malignancies through propensity score-matched cohort studies. METHODS: The PubMed, Embase, and Cochrane databases were searched using Medical Subject Headings terms and keywords from inception until May 31, 2023. The quality of the included studies was assessed using the Newcastle-Ottawa quality assessment scale. The mean difference with 95% confidence interval (95% CI) was used for analysis of continuous variables; the risk ratio with 95% CI was used for dichotomous variables; and the hazard ratio with 95% CI was used for survival-related variables. Meta-analysis was performed using a random-effects model. RESULTS: Five high-quality cohort studies with 986 patients were included (370 and 616 cases for RLR and LLR, respectively). In terms of surgical outcomes, there were no significant differences in the operation time, conversion rate to open surgery, overall complication rate, major complication rate, and length of hospital stay between the RLR and LLR groups. In terms of oncological outcomes, there were no significant differences in the 5-year overall survival and disease-free survival between the two groups. CONCLUSION: Surgical and oncological outcomes are comparable between RLR and LLR on patients with liver malignancies. Therefore, the benefits of applying RLR in patients with liver malignancies need to be further explored.
作者机构：
[Min, Junxia; Yu, Yingying; Wang, Fudi; Liu, Yutong; Zhou, Jiahui; Yue, Wuyang; Su, Yunxing; Yang, Sisi; Li, Xiaopeng; Min, JX; Sun, Shumin] Zhejiang Univ, Affiliated Hosp 1, Affiliated Hosp 2, Inst Translat Med,Sch Med, Hangzhou 310058, Peoples R China.;[Yu, Yingying; Wang, Fudi; Lin, Zhiting] Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Shah, YM; Shah, Yatrik M.; Das, Nupur K.] Univ Michigan, Div Gastroenterol, Internal Med, Ann Arbor, MI 48109 USA.;[Shah, YM; Shah, Yatrik M.; Das, Nupur K.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.;[Wu, Qian] Zhejiang Univ, Int Inst Med, Sch Med, Yiwu, Zhejiang, Peoples R China.
通讯机构：
[Wang, FD ; Min, JX] Z;[Shah, YM ] U;Zhejiang Univ, Affiliated Hosp 1, Affiliated Hosp 2, Inst Translat Med,Sch Med, Hangzhou 310058, Peoples R China.;Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Univ Michigan, Div Gastroenterol, Internal Med, Ann Arbor, MI 48109 USA.
关键词：
FG-4592;HIF;anemia of inflammation;chemotherapy-induced anemia;hypoxia;iron-refractory iron deficiency anemia
摘要：
In clinics, hepcidin levels are elevated in various anemia-related conditions, particularly in iron-refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron-refractory anemia, the potential effect of hypoxia and pharmacologically-mimetic drug FG-4592 (Roxadustat) are evaluated, a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor, on mouse models of iron-refractory iron-deficiency anemia (IRIDA), anemia of inflammation and 5-fluorouracil-induced chemotherapy-related anemia. The potent protective effects of both hypoxia and FG-4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG-4592 could stabilize duodenal Hif2 alpha, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin-activated anemias. Moreover, duodenal Hif2 alpha overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2 alpha knockout in the gut significantly delays the recovery from 5-fluorouracil-induced anemia, which can not be rescued by FG-4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia-related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia. In this article, it is demonstrated that targeting the duodenal Hif2 alpha-Fpn axis as a novel strategy to improve refractory hepcidin-activated anemias, including iron-refractory iron-deficiency anemia (IRIDA), inflammatory anemia and chemotherapy-induced anemia, in mice, which provides compelling evidence for further clinical translation.image
