1.Targeting lactic acidosis in the tumor microenvironment: Enhancing TACE efficacy in hepatocellular carcinoma
Shuyi Hao ; Hong Yao ; Haojie Yu ; Lijun Wang ; Tingdong Yu ; Hongping Xia ; Yong Zha
Liver Research 2025;9(4):273-285
Lactic acidosis is a hallmark of the tumor microenvironment (TME) and a critical impediment to the efficacy of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Incomplete embolization preserves viable tumor cells that amplify hypoxia-driven glycolysis, generating a lactic acid-rich milieu that drives treatment resistance, skews immune populations toward immunosuppressive phenotypes, and impairs cytotoxic T lymphocyte function. In this review, we elucidate the pathways through which lactic acidosis compromises TACE efficacy and propose novel strategies for its mitigation. We examine emerging approaches, including systemic or intra-arterial alkalization, targeted inhibition of lactate production and export, and calcium carbonate nanoparticles, and evaluate their respective merits and limitations. Finally, we propose a combination regimen of calcium carbonate nanoparticles, lactate-targeting agents, and TACE to achieve precise drug delivery, synergistic lactic acid depletion, and enhanced antitumor immunity. These integrated strategies have the potential to convert immunologically “cold” HCC lesions into “hot” ones, thereby improving TACE outcomes and disease control.
2.Nicotinic acid protects against hepatic ischemia-reperfusion injury via suppressing mitochondrial damage-induced ferroptosis
Qian Zeng ; Yina Sun ; Mengzhen Lei ; Zihan Liu ; Xijing Yan ; Rong Li ; Jun Zheng ; Jiandong Zha ; Lijun Zhang ; Xiaoling Guan ; Jia Yao
Liver Research 2025;9(4):324-337
Abstract
Background and aims
Hepatic ischemia-reperfusion injury (HIRI) is a major contributor to liver dysfunction and failure, particularly in the context of liver transplantation. Its pathogenesis is primarily driven by ferroptosis, oxidative stress, and mitochondrial dysfunction. Given the interplay among these mechanisms through redox imbalance and disrupted energy metabolism, nicotinic acid (NA)—recognized for its antioxidative and metabolic regulatory properties—emerges as a promising therapeutic candidate. This study aims to investigate the protective effects of NA on HIRI and elucidate its underlying mechanisms.
Methods
An HIRI model in mice and a hypoxia/reoxygenation (H/R) model in primary hepatocytes were established to evaluate the effects of NA treatment on oxidative stress. NA was administered prior to model induction. N-acetylcysteine (NAC) was used as a comparator. Comprehensive assessments of ferroptosis, oxidative stress, mitophagy, and mitochondrial biogenesis markers were conducted using Western blotting, immunohistochemistry, immunofluorescence, and biochemical assays.
Results
NA pretreatment reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (LDH) levels, suppressed inflammation by decreasing neutrophil infiltration and macrophage activation, and mitigated oxidative stress by lowering reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It enhanced antioxidant defenses, inhibited ferroptosis, and improved mitochondrial health through increased mitophagy, mitochondrial biogenesis, and mitochondrial permeability transition pore (mPTP) stabilization, leading to enhanced ATP production and mitochondrial function in HIRI.
Conclusions
NA improves mitochondrial function by promoting mitophagy and mitochondrial biogenesis, which reduces ferroptosis and oxidative stress, thereby alleviating HIRI.
3.Development of clinical practice guidelines for the management of adherence to highly active antiretroviral therapy
Liang FU ; Yan HU ; Hongzhou LU ; Meijuan BAO ; Lin ZHANG ; Yinzhong SHEN ; Lijun ZHA ; Cheng′en PAN ; Huiwen LI ; Zheng ZHU ; Ning DONG ; Yanjuan GAN
Chinese Journal of Practical Nursing 2016;32(19):1497-1501
Objective To develop the clinical practice guidelines for the management of medication adherence to highly active antiretroviral therapy (HAART) in China. Methods The development methods included qualitative interview of 31 stakeholders, questionnaire survey of 423 PLHIV, adaptation of 30 clinical practice guidelines related to AIDS care, and overviews of reviews of 44 systematic reviews/Meta-analysis. Results 10 clinical practice guidelines and 10 systematic reviews/Meta-analysis were included. The clinical practice guidelines for the management of HAART were formed. Conclusions The formed clinical practice guidelines showed better applicability and higher general quality. It is recommended to use the guidelines in AIDS care.
4.Application of negative pressure puncture without the cuff in staphylococal scalded skin syndrome
Lijun JIANG ; Yongmei GAN ; Yufang ZHA
Chinese Journal of Practical Nursing 2011;27(23):47-49
Objective To discuss the effect of negative pressure puncture without the cuff in staphylococal scalded skin syndrome (SSSS). Methods 68 children with SSSS in our department were chosen as research subjects from January 2009 to December 2010, and then were divided into the experimental group and the control group randomly. All children used the distal upper limbs for superficial vein puncture. The control group used vein puncture and catheter fixation by conventional methods, the experimental group used negative pressure puncture without the cuff in order to improve the methods for filling and indwelling intravenous needle fixation. Results In the experimental group, the parent satisfaction degree and the average catheter indwelling time were significantly better than the control group, the adverse reactions were lower than the control group. Success rate of one-time puncture and rate of venous blood return showed no significant difference compared with the control group. Conclusions The method of negative pressure puncture without the cuff is simple, easy to grasp and has a high puncture success rate, is better protection of skin and blood vessels for children with staphylococal scalded skin syndrome.
5.Evaluation of non-critical coronary stenosis by coherent contrast imaging
Xiaolin CHEN ; Tingting LIU ; Lijun TANG ; Zhehong YU ; Dahui WEN ; Daogang ZHA ; Yili LIU
Chinese Journal of Ultrasonography 2009;18(11):977-979
Objective To investigate whether non-critical coronary stenosis can be detected by coherent contrast imaging(CCI) at rest without stress.Methods Three degrees of stenosis were made in left anterior descending of 12 dogs.Myocardial contrast echocardiography(MCE) was performed with CCI and the correlation among the variables of MCE curve and the degrees of stenosis were analyzed by cubic regression.Results The time to peak was significantly prolonged with progressive coronary stenosis (P<0.01) and related to the degree of stenosis (R~2=0.991,P<0.001).Conclusions CCI could be used to detected non-critical coronary stenosis at rest without stress.


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