1.Clinical study on noninfectious fever of endovascular aortic repair
Zhengyue QIAN ; Yao FU ; Wenbo ZHOU ; Bingbing MA
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):275-280
Objective To analyze the clinical characteristics and risk factors of noninfectious fever after endovascular repair of aortic dilatation diseases, and to explore management strategies. Methods A retrospective analysis was conducted on the clinical data of patients who underwent endovascular aortic repair for aortic dilatation diseases from January 2021 to October 2023. Based on inclusion and exclusion criteria, the enrolled patients were divided into a febrile group and an afebrile group according to the presence of postoperative fever. Clinical data, including demographics and surgical details, were compared between the two groups. Multivariate logistic regression analysis was performed on indicators with P≤0.05 in the univariate analysis, and receiver operating characteristic (ROC) curves were generated to analyze the predictive value of risk factors for postoperative noninfectious fever. Results A total of 305 patients were included in the final analysis. Postoperative noninfectious fever occurred in 75.08% (229/305) of the patients, with 98.25% of cases occurring within the first two postoperative days. The febrile group (n=229) had a median age of 65.0 (IQR: 53.0, 73.0) years with 83.4% males, while the afebrile group (n=76) had a median age of 71.0 (IQR: 65.0, 76.7) years with 84.2% males. Univariate analysis showed that the age, prevalence of coronary heart disease, preoperative statin use, and prevalence of aortic aneurysm were significantly lower in the febrile group compared to the afebrile group. Logistic regression analysis indicated that age, surgical site, disease type, preoperative elevated body temperature, and stent type were significantly associated with noninfectious fever, while preoperative statin use was negatively correlated. ROC curve analysis demonstrated that age, surgical site, preoperative elevated body temperature, and stent type had significant predictive value for postoperative noninfectious fever (P<0.01). Conclusion Noninfectious fever is highly prevalent following aortic repair. The relationship between fever and infection should be comprehensively evaluated based on risk factors and changes in the patient's condition to promote the rational use of antibiotics.
2.Integrating Transcriptomics and 3D Organoids to Investigate Mechanism of Periplaneta americana Extract Against Lung Adenocarcinoma
Qiong MA ; Chunxia HUANG ; Jiawei HE ; Yuting BAI ; Xingyue LIU ; Yuxuan XIONG ; Yang ZHONG ; Hengzhou LAI ; Yuling JIANG ; Xueke LI ; Qian WANG ; Yifeng REN ; Xi FU ; Funeng GENG ; Taoqing WU ; Ping XIAO ; Fengming YOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):124-132
ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract(PAE) against human-derived lung adenocarcinoma organoids(LUAD-PDOs) and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid(Nor-PDOs) models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8(CCK-8) assay. Experimental groups included the model group(LUAD-PDOs), normal group, model administration group(LUAD-PDOs+PAE), and normal administration group(Nor-PDOs+PAE). Hematoxylin-eosin(HE) staining was used to observe the pathological structures of PDOs, immunohistochemistry(IHC) was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7(CK-7) and Napsin A, TUNEL staining was applied to detect cell apoptosis. RNA sequencing(RNA-Seq) was conducted to identify differentially expressed genes(DEGs), followed by Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and Gene Set Enrichment Analysis(GSEA), alongside protein-protein interaction(PPI) network analysis to screen core mechanisms. Finally, key targets were validated by integrating external database analysis with immunofluorescence(IF). ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures, whereas LUAD-PDOs displayed dense, solid structures. CCK-8 and TUNEL assays revealed that, compared with the model group, PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells, while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention(347 up-regulated and 372 down-regulated)(P<0.05). GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism, including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway(P<0.05). PPI network analysis indicated that breast cancer type 1 susceptibility protein(BRCA1) and checkpoint kinase 1(CHEK1) were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention(P<0.05). Furthermore, survival analysis based on The Cancer Genome Atlas(TCGA) database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD(P<0.05). ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis, its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway, with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.
3.Correlation between spinal sagittal imbalance and knee joint parameters detected by whole-body EOS imaging
Feng ZHOU ; Pengfei FU ; Yufan QIAN ; Pingcheng XU ; Jiongjiong GUO ; Lei ZHANG
Chinese Journal of Tissue Engineering Research 2026;30(3):596-603
BACKGROUND:With changing lifestyles and aging,sagittal spinal imbalance has become a common orthopedic issue significantly affecting knee and pelvic function.Understanding the impact of sagittal spinal imbalance and its compensatory mechanisms is crucial for improving the clinical management of chronic pain.OBJECTIVE:To evaluate the alignment of the spine-pelvis-lower extremities using whole-body EOS imaging,analyze the correlation between spinal sagittal imbalance and knee joint parameters,and explore their compensatory mechanisms.METHODS:A total of 71 patients with chronic low back pain or patellofemoral pain who visited Department of Orthopedics,First Affiliated Hospital of Soochow University between January 1,2021 and December 31,2023 were included.Radiographic measurements were performed using whole-body EOS to determine pelvic tilt,pelvic incidence,lumbar lordosis,sagittal vertical axis,global tilt,hip-knee-angle,knee flexion angle,lateral distal femoral angle,and medial proximal tibial angle.Patients were classified into normal group(pelvic incidence-lumbar lordosis<10°),compensated group(10°<pelvic incidence-lumbar lordosis<20°),and decompensated group(pelvic incidence-lumbar lordosis>20°)based on the SRS-Schwab spinal deformity classification according to pelvic incidence-lumbar lordosis difference.The differences in radiographic parameters among the groups were analyzed.The differences in American Knee Society Knee Score and Oswestry Disability Index scores were compared among each group.Patients were divided into chronic low back pain group and non-chronic low back pain group,patellofemoral pain group and non-patellofemoral pain group based on clinical symptoms,and the relationship between radiographic parameter differences and clinical symptoms was analyzed.RESULTS AND CONCLUSION:(1)When pelvic incidence-lumbar lordosis was less than 20°,lateral distal femoral angle and medial proximal tibial angle tended to stabilize.When pelvic incidence-lumbar lordosis was greater than 20°,it showed a linear correlation with lateral distal femoral angle and medial proximal tibial angle,with lateral distal femoral angle increasing and medial proximal tibial angle decreasing with increasing pelvic incidence-lumbar lordosis values.(2)Compared with the normal group,the compensated group had significantly increased pelvic tilt(P<0.01),while knee joint parameters hip-knee-angle and knee flexion angle showed no significant differences;the decompensated group showed significant increases in pelvic tilt(P<0.01),and decreases in hip-knee-angle,and knee flexion angle(P<0.01).Compared with the compensated group,the decompensated group showed a significant decrease in hip-knee-angle(P<0.05),but had no significant differences in pelvic tilt and knee flexion angle.(3)Compared with the non-patellofemoral pain group,patients with patellofemoral pain had significant decreases in spinal lumbar lordosis,lateral distal femoral angle,and medial proximal tibial angle(P<0.05)and a significant increase in pelvic incidence-lumbar lordosis(P<0.05).(4)Patients with low back pain had significant differences in radiographic parameters compared with the non-chronic low back pain group(P<0.05).(5)Compared with the normal group,both the compensated and decompensated groups showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P<0.05).Compared with the compensated group,the decompensated group showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P<0.05).(6)Pelvic incidence-lumbar lordosis values increased with age and were higher in females compared with males.(7)This study systematically reveals the spine and lower limbs play an important role in disease progression and clinical symptoms.Associated symptoms low back pain and patellofemoral pain are related to the stability of the spine-pelvis-lower extremity alignment.Furthermore,spinal sagittal imbalance is more severe in elderly and female patients.
4.Correlation between spinal sagittal imbalance and knee joint parameters detected by whole-body EOS imaging
Feng ZHOU ; Pengfei FU ; Yufan QIAN ; Pingcheng XU ; Jiongjiong GUO ; Lei ZHANG
Chinese Journal of Tissue Engineering Research 2026;30(3):596-603
BACKGROUND:With changing lifestyles and aging,sagittal spinal imbalance has become a common orthopedic issue significantly affecting knee and pelvic function.Understanding the impact of sagittal spinal imbalance and its compensatory mechanisms is crucial for improving the clinical management of chronic pain.OBJECTIVE:To evaluate the alignment of the spine-pelvis-lower extremities using whole-body EOS imaging,analyze the correlation between spinal sagittal imbalance and knee joint parameters,and explore their compensatory mechanisms.METHODS:A total of 71 patients with chronic low back pain or patellofemoral pain who visited Department of Orthopedics,First Affiliated Hospital of Soochow University between January 1,2021 and December 31,2023 were included.Radiographic measurements were performed using whole-body EOS to determine pelvic tilt,pelvic incidence,lumbar lordosis,sagittal vertical axis,global tilt,hip-knee-angle,knee flexion angle,lateral distal femoral angle,and medial proximal tibial angle.Patients were classified into normal group(pelvic incidence-lumbar lordosis<10°),compensated group(10°<pelvic incidence-lumbar lordosis<20°),and decompensated group(pelvic incidence-lumbar lordosis>20°)based on the SRS-Schwab spinal deformity classification according to pelvic incidence-lumbar lordosis difference.The differences in radiographic parameters among the groups were analyzed.The differences in American Knee Society Knee Score and Oswestry Disability Index scores were compared among each group.Patients were divided into chronic low back pain group and non-chronic low back pain group,patellofemoral pain group and non-patellofemoral pain group based on clinical symptoms,and the relationship between radiographic parameter differences and clinical symptoms was analyzed.RESULTS AND CONCLUSION:(1)When pelvic incidence-lumbar lordosis was less than 20°,lateral distal femoral angle and medial proximal tibial angle tended to stabilize.When pelvic incidence-lumbar lordosis was greater than 20°,it showed a linear correlation with lateral distal femoral angle and medial proximal tibial angle,with lateral distal femoral angle increasing and medial proximal tibial angle decreasing with increasing pelvic incidence-lumbar lordosis values.(2)Compared with the normal group,the compensated group had significantly increased pelvic tilt(P<0.01),while knee joint parameters hip-knee-angle and knee flexion angle showed no significant differences;the decompensated group showed significant increases in pelvic tilt(P<0.01),and decreases in hip-knee-angle,and knee flexion angle(P<0.01).Compared with the compensated group,the decompensated group showed a significant decrease in hip-knee-angle(P<0.05),but had no significant differences in pelvic tilt and knee flexion angle.(3)Compared with the non-patellofemoral pain group,patients with patellofemoral pain had significant decreases in spinal lumbar lordosis,lateral distal femoral angle,and medial proximal tibial angle(P<0.05)and a significant increase in pelvic incidence-lumbar lordosis(P<0.05).(4)Patients with low back pain had significant differences in radiographic parameters compared with the non-chronic low back pain group(P<0.05).(5)Compared with the normal group,both the compensated and decompensated groups showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P<0.05).Compared with the compensated group,the decompensated group showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P<0.05).(6)Pelvic incidence-lumbar lordosis values increased with age and were higher in females compared with males.(7)This study systematically reveals the spine and lower limbs play an important role in disease progression and clinical symptoms.Associated symptoms low back pain and patellofemoral pain are related to the stability of the spine-pelvis-lower extremity alignment.Furthermore,spinal sagittal imbalance is more severe in elderly and female patients.
5.Impact of infusion of red blood cell suspension at different perioperative periods in patients with valvular heart disease: A propensity score matching study
Shan XU ; Bo FU ; Ao WEI ; Qian ZHANG ; Yaqing CAO ; Nan JIANG ; Zhigang GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(05):772-777
Objective To investigate the impact of red blood cell suspension infusion across various perioperative periods on patients with valvular heart disease. Methods The patients with valvular heart disease admitted to Tianjin Chest Hospital from 2018 to 2020 were selected. Based on the timing of perioperative red cell suspension infusion, patients were categorized into three groups: a group 1 receiving intraoperative red cell suspension infusion, a group 2 receiving red cell suspension infusion within 24 hours after entering the ICU, and a group 3 receiving red cell suspension infusion at both time points. The laboratory results, perioperative blood component infusion volume, and other relevant parameters were retrospectively analyzed. After propensity score matching, the differences in different variables among the three groups were compared. Results After propensity score matching, 102 patients were enrolled, including 52 males and 50 females, with an average age of (61.74±10.58) years. There were 34 patients in each group. The preoperative hemoglobin (Hb) value of the group 2 was significantly higher than that of the group 1 and the group 3, and the amount of red cell suspension and autoblood transfusion was the lowest (P<0.05). Group 1 had the highest postoperative Hb, as well as the highest Hb and hematocrit (HCT) levels within 24 hours post-surgery (P<0.05). The group 1 had the lowest plasma, platelet and cryoprecipitate infusion volumes, and the shortest cardiopulmonary bypass time, aortic occlusion time, postoperative ICU stay and hospital stay, and the least blood loss and total drainage volume (P<0.05). The difference between postoperative and preoperative Hb (△Hb1) was highest in group 1 (P<0.05). Conclusion For patients with valvular heart disease, intraoperative-only infusion of red blood cell suspension is associated with a better prognosis at discharge and during follow-up.
6.Effect of Heat-sensitive Moxibustion on Quality of Life and Immune Function in Non-Small Cell Lung Cancer Patients with Qi Deficiency and Phlegm Stasis Syndrome Undergoing Chemotherapy:A Randomized Controlled Trial
Wenhao ZHAN ; Qian DING ; Zhiwei DONG ; Ting LI ; Shumei FU ; Ning TIAN
Journal of Traditional Chinese Medicine 2026;67(12):1289-1296
ObjectiveTo observe the effect of heat-sensitive moxibustion on quality of life and immune function in non-small cell lung cancer (NSCLC) patients undergoing chemotherapy. MethodsSeventy NSCLC patients with qi deficiency and phlegm stasis syndrome were randomly divided into an intervention group and a control group, with 35 cases in each group. The control group received chemotherapy combined with routine symptomatic treatment, while the intervention group additionally received heat-sensitive moxibustion since the first day of chemotherapy. Acupoints included Dazhui (GV14), bilateral Feishu (BL13), Zhongwan (CV12), Qihai (CV6), and Guanyuan (CV4). The site exhibiting the strongest heat-sensitization response was selected for moxibustion. Treatment was administered for 45 minutes per session, three times weekly for three consecutive weeks, totaling nine sessions. Before and after treatment, quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and traditional Chinese medicine (TCM) syndrome scores were evaluated. Peripheral blood levels of natural killer (NK) cells and T-lymphocyte subsets including CD3+, CD4+, and CD8+, and CD4+/CD8+ ratio were measured. Levels of programmed cell death protein-1 (PD-1), including PD-1⁺CD4⁺ and PD-1⁺CD8⁺ cells, were also assessed. Liver and renal function were monitored before and after treatment, and adverse events were recorded. ResultsIn the intervention group, 1 participant withdrew and 1 was excluded, while in the control group, 2 participants withdrew. Ultimately, 33 participants in each group were included in the final analysis. The intervention group showed significant improvements in physical, role, emotional, cognitive, and social functioning, as well as global health status after treatment, while scores for fatigue, nausea and vomiting, dyspnea, appetite loss, diarrhea, and TCM syndrome scale were significantly decreased (P<0.05). Moreover, the intervention group demonstrated higher scores in physical functioning, role functioning, and global health status, as well as lower scores for fatigue, nausea and vomiting, dyspnea, appetite loss, diarrhea, and the TCM syndrome scale than the control group (P<0.05). After treatment, the levels of peripheral NK cells and PD-1⁺CD8⁺ T cells in the intervention group increased significantly; furthermore, the intervention group exhibited higher peripheral NK cell levels and lower PD-1⁺CD8⁺ T cell levels than the control group (P<0.05). No significant differences were found in liver or renal function between the two groups (P>0.05). In addition, no adverse events such as burns or moxibustion-induced syncope occurred during the study. ConclusionHeat-sensitive moxibustion as an adjunctive therapy may enhance immune function, alleviate clinical symptoms, and improve quality of life, while demonstrating a favorable safety profile in NSCLC patients with qi deficiency and phlegm stasis.
7.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
8.Post-exposure prophylaxis and follow-up in children and young persons presenting with sexual assault.
Sarah Hui Wen YAO ; Karen NADUA ; Chia Yin CHONG ; Koh Cheng THOON ; Chee Fu YUNG ; Natalie Woon Hui TAN ; Kai-Qian KAM ; Peter WONG ; Juliet TAN ; Jiahui LI
Annals of the Academy of Medicine, Singapore 2025;54(7):410-418
INTRODUCTION:
Paediatric sexual assault (SA) victims should be assessed for post-exposure prophylaxis (PEP) to mitigate the risk of sexually transmitted infections (STIs). We describe the clinical characteristics of children and young persons (CYPs) presenting with SA at KK Women's and Children's Hospital in Singapore, viral PEP (human immunodeficiency virus [HIV] and hepatitis B virus [HBV]) prescribing practices, and STI evaluation at follow-up.
METHOD:
Medical records of CYPs ≤16 years who presented with SA between January 2022 and August 2023 were reviewed, including assault and assailant characteristics, baseline and follow-up STI screening, PEP prescription, adherence and follow-up attendance. CYPs with SA in the preceding 72 hours by HIV-positive or HIV-status unknown assailants with high-risk characteris-tics were eligible for HIV PEP.
RESULTS:
We analysed 278 CYPs who made 292 SA visits. There were 40 (13.7%) CYPs eligible for HIV PEP, of whom 29 (82.9%) received it. Among those tested at baseline, 9% and 34.9% of CYPs tested positive for Chlamydia trachomatis and Gardnerella vaginalis, respectively. None tested positive for Neisseria gonorrhoeae, Trichomonas vaginalis, HIV, HBV or hepatitis C. Majority of CYPs tested were HBV non-immune (n=167, 67.6%); only 77 (46.1%) received the vaccine. Out of 27 CYPs eligible for HBV PEP with immunoglobulin, only 21 (77.7%) received immunoglobulin. A total of 37 CYPs received HIV PEP, including 8 who were retrospectively deemed ineligible. Only 10 (27%) completed the course. Overall, 153 (57.7%) CYPs attended follow-up, and none seroconverted for HIV or HBV.
CONCLUSION
We report suboptimal rates of HBV post-exposure vaccination, and low compliance to HIV PEP and follow-up among paediatric SA victims. Factors contri-buting to poor compliance should be examined to optimise care for this vulnerable population.
Humans
;
Post-Exposure Prophylaxis/methods*
;
Female
;
Child
;
Adolescent
;
Singapore/epidemiology*
;
HIV Infections/prevention & control*
;
Male
;
Sexually Transmitted Diseases/epidemiology*
;
Retrospective Studies
;
Hepatitis B/prevention & control*
;
Follow-Up Studies
;
Child, Preschool
;
Sex Offenses/statistics & numerical data*
;
Child Abuse, Sexual
9.Lactate metabolism and acute kidney injury.
Hui LI ; Qian REN ; Min SHI ; Liang MA ; Ping FU
Chinese Medical Journal 2025;138(8):916-924
Acute kidney injury (AKI) is a common clinically critical syndrome in hospitalized patients with high morbidity and mortality. At present, the mechanism of AKI has not been fully elucidated, and no therapeutic drugs exist. As known, glycolytic product lactate is a key metabolite in physiological and pathological processes. The kidney is an important gluconeogenic organ, where lactate is the primary substrate of renal gluconeogenesis in physiological conditions. During AKI, altered glycolysis and gluconeogenesis in kidneys significantly disturb the lactate metabolic balance, which exert impacts on the severity and prognosis of AKI. Additionally, lactate-derived posttranslational modification, namely lactylation, is novel to AKI as it could regulate gene transcription of metabolic enzymes involved in glycolysis or Warburg effect. Protein lactylation widely exists in human tissues and may severely affect non-histone functions. Moreover, the strategies of intervening lactate metabolic pathways are expected to bring a new dawn for the treatment of AKI. This review focused on renal lactate metabolism, especially in proximal renal tubules after AKI, and updated recent advances of lactylation modification, which may help to explore potential therapeutic targets against AKI.
Humans
;
Acute Kidney Injury/metabolism*
;
Lactic Acid/metabolism*
;
Animals
;
Glycolysis/physiology*
;
Gluconeogenesis/physiology*
;
Kidney/metabolism*
10.Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.
Chaoqun WANG ; Hongjun YU ; Shounan LU ; Shanjia KE ; Yanan XU ; Zhigang FENG ; Baolin QIAN ; Miaoyu BAI ; Bing YIN ; Xinglong LI ; Yongliang HUA ; Zhongyu LI ; Dong CHEN ; Bangliang CHEN ; Yongzhi ZHOU ; Shangha PAN ; Yao FU ; Hongchi JIANG ; Dawei WANG ; Yong MA
Chinese Medical Journal 2025;138(22):2993-3003
BACKGROUND:
Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.
METHODS:
In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy.
RESULTS:
A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent.
CONCLUSION
Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals
;
Arsenic Trioxide
;
Autophagy/physiology*
;
Reperfusion Injury/prevention & control*
;
Mice
;
Male
;
Proto-Oncogene Proteins c-akt/physiology*
;
Arsenicals/therapeutic use*
;
Oxides/therapeutic use*
;
Liver/metabolism*
;
Extracellular Signal-Regulated MAP Kinases/metabolism*
;
Mice, Inbred C57BL


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