1.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
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Arsenic Trioxide
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Autophagy/physiology*
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Reperfusion Injury/prevention & control*
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Mice
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Male
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Proto-Oncogene Proteins c-akt/physiology*
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Arsenicals/therapeutic use*
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Oxides/therapeutic use*
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Liver/metabolism*
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Extracellular Signal-Regulated MAP Kinases/metabolism*
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Mice, Inbred C57BL
2.Characteristics of brain activation during treadmill walking with visual feedback in healthy subjects and hemiple-gic patients:a functional near infrared spectroscopy study
Dandan XIE ; Shanjia CHEN ; Lei LEI ; Guo YU ; Jiahui YU ; Jiapei ZHAO ; Xiaokuo HE
Chinese Journal of Rehabilitation Theory and Practice 2024;30(9):1074-1081
Objective To compare the cortical activation characteristic in the healthy subjects and hemiplegia patients during execut-ing treadmill walking with visual feedback(TWVF). Methods From August to November,2021,eight stroke patients with right hemiplegia(patient group)and eight healthy subjects(healthy group)in Fifth Hospital of Xiamen were recruited.Both groups wore functional near-infrared spectroscopy(fNIRS)caps and executed TWVF,respectively.Experimental block design for walking modes in-cluded the preparation period(10 s)and task period(five cycles of"step 30 s-rest 30 s").The cortical activation(β values)were measured.The regions of interest(ROI)included the pre-motor cortex(PMC),supplementary motor area(SMA),primary motor cortex(M1),primary somatosensory cortex(S1)and sensorimotor cortex(SMC,M1+S1). Results No activation in bilateral M1,and some significant activation(P<0.05)in the left hemisphere SAM,PMC and S1,were found during walking in the healthy group.M1 was activated more in the unaffected(right)hemisphere than in the affected(left)hemisphere during walking in the patient group(P<0.05),and less PMC activation was found(P<0.05).M1 in bilateral hemispheres,SMA in the unaffected hemisphere and PMC in the affected hemi-sphere were activated more in the patient group than in the healthy group(P<0.05). Conclusion The locomotor network of SMC-PMC-SMA are activated more in the hemiplegic patients than in the healthy pepole during walking.M1 are almost not activated in the healthy people during walking,and compensa-torily activated in M1 of the unaffected side in the hemiplegic patients.
3.The effect of functional electrical stimulation on the contraction pattern of lower limbs muscle in stroke patients in convalescent stage
Xiaokuo HE ; Shanjia CHEN ; Xiao LIN
Chinese Journal of Rehabilitation Medicine 2024;39(10):1462-1467
Objective:To observe the effect of functional electrical stimulation(FES)in walking mode on the lower limb muscle contraction pattern of stroke patients. Method:Thirty patients with hemiplegia in the convalescent stage were included.Electrodes were placed on 4 motion points:the hemiplegic tibialis anterior,quadriceps femoris,gastrocnemius and hamstring muscles respec-tively.The patients walked with FES machine and received electrical stimulation.The surface electromyogram(sEMG)signals were collected on 4 different time:pre-treatment,treatment at 5 min,10 min,and 15 min respectively.Median frequency(MDF)of electromyography reflected the current trend of muscle fatigue,and the co-contraction ratio(CI)showed for contraction pattems of antagonistic muscles in extension of knee and ankle-back,through analyzing the sEMG signals changes of 4 motion points muscle in active contraction.Rat-ed perceived fatigue Exertion(RPE)was used to evaluate the patients'fatigue feeling at 4 time points. Result:The CI of the gastrocnemius muscle during ankle dorsiflexsion and hamstring muscles during knee ex-tension were significantly reduced in electrical stimulation group at 5min and 10min after walking than in the pre-treatment and pseudo-stimulation control groups(P<0.05);however,the CI of antagonist muscles increased after 15min of the treatment,especially the CI of the hamstring muscles during knee extension was not signifi-cantly different from that before treatment(P>0.05).The MDF values of tibialis anterior,gastrocnemius,rectus femoris and hamstring muscles in the electrical stimulation group were significantly lower at 5 min,10 min and 15 min of the treatment compare with the pre-treatment and control group(P<0.05).The MDF value was lower with longer stimulate time,while the control group was significantly lower at 15-min of pesudo-stimula-tion than the level before treatment(P<0.05).No patients reported fatigue before and after walking with wear-ing FES machine for 5 min,but did after 10 min and 15 min in both groups.The percentages of the patents who reported fatigue in electrical stimulation group at 10min and 15min were higher than that of the control group(40%,80%vs 20%,40%). Conclusion:Functional electrical stimulation for 5-10min can significantly improve the contraction pattern of lower limbs muscle,but the declining muscular coordination when knee extension and ankle dorsiflexsion after 15min stimulation,especially rectus femoris and hamstrings.It is recommended that the walking duration with electrical stimulation machine should not exceed 15 min,in order to avoid the aggravation of fatigue affecting the therapeutic effect of FES treatment.
4.The characteristics of cortical activation when hemiplegic stroke survivors walk assisted by functional electrical stimulation
Xiaokuo HE ; Lei LEI ; Guo YU ; Dewang SHEN ; Xin LIN ; Shanjia CHEN
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(9):774-778
Objective:To explore the characteristics of cortical activation during the stimulation-assisted walking of hemiplegic stroke survivors using functional near-infrared spectroscopy (fNIRS).Methods:Eight stroke survivors with right hemiplegia (average age 44.4±7.2 years) in a self-controlled study each walked at 2km/h on a treadmill, alone and assisted by functional electronic stimulation (FES). Real-time near-infrared spectroscopic images were recorded. The Matlab NIRS-SPM toolkit was employed to calculate the changes in oxyhemoglobin concentration in different cortical regions. A general linear model was evaluated which integrated the task effects, and version 20.0 of the SPSS statistical software was used to perform single sample or paired sample t-tests of the beta values so as to produce activation hot maps of the significant differences.Results:During unassisted walking channels 8, 10, 11, 13-20, 23-28, 30 and 32-37 were significantly activated. During FES-assisted walking it was the same channels plus channels 9 and 22, 31. The results suggest that in walking the cortical regions activated are mainly located in M1 of the unaffected hemisphere, supplemented by M1 and SMA, PMC and S1 in the affected hemisphere. There were significant differences in the activation of channels 9, 24, 27, 32, 33 between the two walking tasks. FES-assistance enhances S1 activation on the unaffected side, as well as the SMA and PMC of the affected side more significantly.Conclusions:Bilateral asymmetrical activation is found mostly in M1 during walking with or without FES assistance. FES assistance significantly strengthens the compensatory activation of the PMC and SMA of the affected hemisphere while walking for those with hemiplegia.
5.Progress in diagnosis and selection of drug resistance therapy for childhood tuberculosis
Chinese Journal of Applied Clinical Pediatrics 2019;34(6):472-474
Diagnosis of tuberculosis in children is challenging. Traditional and molecular microbiologic methods lack sensitivity,particularly in children. With the development of science and technology,more and more testing me﹣thods are applied in clinical practice,so that tuberculosis(TB)can be diagnosed in time and treated at the right time. TB is still one of the most difficult infectious diseases to treat,and the second most frequent cause of death due to infec﹣tious disease throughout the World. The number of cases of multidrug - resistant TB( MDR - TB)and extensively drug-resistant TB(ⅩDR-TB),Which are characterized by high mortality rates,is increasing. Therefore,appropriate drug selection is particularly critical in the treatment of drug-resistant tuberculosis.
6.Clinical diagnosis and treatment of bronchial foreign bodies in 147 children
Shanjia CHEN ; Haoxiang GU ; Min LU ; Beirong WU ; Rong TANG
Journal of Clinical Pediatrics 2019;37(1):26-29
Objective To explore the clinical characteristics of bronchial foreign bodies in children. Method The clinical data of 147 children with exogenous bronchial foreign body admitted between 2014 and 2016 were retrospectively analyzed, and the applications of rigid bronchoscopy and flexible bronchoscopy for foreign body extraction were compared. Results All 147 cases were diagnosed with bronchial foreign bodies by chest CT, chest X-ray or respiratory endoscopy. In these cases (104 boys and 43 girls) , 87.8% of whom were aged 1-3 years, the most common types of bronchial foreign body were nuts. The common complications were bronchial mucosal granulation tissue hyperplasia (88 cases, 59.86%) , pneumonia (56 cases, 38.1%) , atelectasis (15 cases, 10.2%) , respiratory failure (14 cases, 9.52%) and bronchiectasis (4 cases, 2.72%) respectively. The foreign bodies were removed by soft bronchoscopy in 106 cases which were successfully removed at one time in 100 cases. Respiratory endoscopy was undergone in 141 cases to remove foreign bodies, and flexible bronchoscope was applied in 106 (72.11%) cases and foreign bodies were successfully removed in first attempt in 100 cases (94.34%) . Rigid bronchoscope was used in 35 cases (23.81%) and foreign bodies were successfully removed in first attempt in 28 cases (80.0%) . Conclusion The majority of children with bronchial foreign body are male. Both flexible and rigid bronchoscopes can remove exogenous foreign bodies in the lower respiratory tract.

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