1.Hydrogen sulfide ameliorates hypoxic pulmonary hypertension in rats by inhibiting aerobic glycolysis-pyroptosis.
Yuan CHENG ; Yun-Na TIAN ; Man HUANG ; Jun-Peng XU ; Wen-Jie CAO ; Xu-Guang JIA ; Li-Yi YOU ; Wan-Tie WANG
Acta Physiologica Sinica 2025;77(3):465-471
The present study aimed to explore whether hydrogen sulfide (H2S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O2) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N2 flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H2S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals
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Rats, Sprague-Dawley
;
Male
;
Hypertension, Pulmonary/metabolism*
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Glycolysis/drug effects*
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Hydrogen Sulfide/therapeutic use*
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Hypoxia/complications*
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Rats
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Pyroptosis/drug effects*
2.Exogenous administration of zinc chloride improves lung ischemia/reperfusion injury in rats.
Shu-Yuan WANG ; Jun-Peng XU ; Yuan CHENG ; Man HUANG ; Si-An CHEN ; Zhuo-Lun LI ; Qi-Hao ZHANG ; Yong-Yue DAI ; Li-Yi YOU ; Wan-Tie WANG
Acta Physiologica Sinica 2025;77(5):811-819
The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl2+I/R group), lung I/R + high-dose ZnCl2 group (HZnCl2+I/R group), lung I/R + medium-dose ZnCl2 group (MZnCl2+I/R group) and TPEN+MZnCl2+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn2+ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl2+I/R group and HZnCl2+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn2+ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn2+ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl2 on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl2 can improve lung I/R injury in rats.
Animals
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Reperfusion Injury/pathology*
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Male
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Rats, Sprague-Dawley
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Rats
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Chlorides/administration & dosage*
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Lung/pathology*
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Zinc Compounds/administration & dosage*
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Apoptosis/drug effects*
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Caspase 3/metabolism*
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Cation Transport Proteins/metabolism*
3.Zinc Oxide-Reduced Graphene Oxide-based Photoelectrochemical Sensor Combined with Molecularly Imprinting Technique for Sensitive Detection of Oxytetracycline
You-Yuan PENG ; Shu-Hong XU ; Qing-Hong PAN
Chinese Journal of Analytical Chemistry 2024;52(2):256-266
In this work,zinc oxide-reduced graphene oxide(ZnO-rGO)nanocomposites were fabricated using hydrothermal method,and the chemical and physical properties of the synthesized ZnO-rGO were characterized by several techniques,including X-ray diffraction and Fourier transform infrared(FT-IR)spectroscopy.A molecularly imprinted photoelectrochemical sensor based on ZnO-rGO was designed for sensitive detection of oxytetracycline(OTC).Polypyrrole(PPy)film was electropolymerized onto ZnO-rGO nanocomposites and OTC molecules were imprinted on the polymer film through hydrogen bonding.After OTC molecules were eluted,the recognition sites for OTC were left on the polymer membrane,enabling the specific detection of OTC.Linear detection of OTC was achieved in the range of 0.1-200 nmol/L with the detection limit of 0.05 nmol/L(S/N=3).The sensor was successfully applied to determination of OTC in milk and honey samples,with recoveries ranging from 95%to 107%.The developed method would provide significant reference value for effective and rapid detection of other antibiotics in the foods.
4.Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities.
Youtao XU ; Qinhong SUN ; Siwei WANG ; Hongyu ZHU ; Guozhang DONG ; Fanchen MENG ; Zhijun XIA ; Jing YOU ; Xiangru KONG ; Jintao WU ; Peng CHEN ; Fangwei YUAN ; Xinyu YU ; Jinfu JI ; Zhitong LI ; Pengcheng ZHU ; Yuxiang SUN ; Tongyan LIU ; Rong YIN ; Lin XU
Chinese Journal of Lung Cancer 2024;26(12):889-900
BACKGROUND:
In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.
METHODS:
A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.
RESULTS:
MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).
CONCLUSIONS
The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans
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Lung Neoplasms/genetics*
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Adenocarcinoma of Lung/genetics*
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China
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Prognosis
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Transcription Factors
5.Risk factors and predictive model of cerebral edema after road traffic accidents-related traumatic brain injury
Di-You CHEN ; Peng-Fei WU ; Xi-Yan ZHU ; Wen-Bing ZHAO ; Shi-Feng SHAO ; Jing-Ru XIE ; Dan-Feng YUAN ; Liang ZHANG ; Kui LI ; Shu-Nan WANG ; Hui ZHAO
Chinese Journal of Traumatology 2024;27(3):153-162
Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.
6.Protective effects of omega-3 polyunsaturated fatty acids on chronic atrophic gastritis of rats
Dun-Huang PENG ; De-Yuan YOU ; Cai-Fa HONG ; Tai-Yong FANG
The Chinese Journal of Clinical Pharmacology 2024;40(2):234-238
Objective To investigate the effect of omega-3 polyunsaturated fatty acids(ω-3 PUFA)on chronic atrophic gastritis of rats.Methods A rat model of chronic atrophic gastritis was established by synthetic method.The rats successfully modeled were randomly divided into model group,experimental-L group,experimental-M group,experimental-H group,positive control group.Normal rats were selected as the normal group.There were 9 rats in each group.Experimental-L,-M,-H groups were given 3,6 and 12 mL·kg-1ω-3 PUFA daily,respectively.The positive control group was given 0.24 g·kg-1 vitacoenzyme suspension daily.Normal group and model group were given the same amount of 0.9%NaCl.Each group was given the drug for 12 weeks.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum interleukin-1 β(IL-1β)level.In situ end labeling staining(TUNEL)was used to detecte the apoptosis of gastric mucosa.Relevant kits were used to detect the level of superoxide dismutase(SOD)and malonaldehyde(MDA).Results IL-1 β levels in normal group,model group,experimental-L,-M,-H groups and positive control group were(58.96±8.23),(140.02±19.65),(109.81±14.35),(98.72±12.64),(85.31±11.42)and(77.64±10.23)pg·mL-1,respectively;apoptotic indices were(7.89±1.36)%,(77.12±10.05)%,(42.33±6.87)%,(31.05±5.29)%,(22.76±4.16)%and(16.89±3.05)%,respectively;SOD levels were(398.71±58.24),(170.25±29.81),(249.81±34.26),(268.04±34.11),(322.15±46.36)and(276.42±29.81)U·mg-1,respectively;MDA levels were(3.55±0.87),(11.02±2.15),(8.02±1.50),(6.92±1.23),(5.98±1.27)and(6.67±1.32)U·mg-1,respectively.Compared with normal group,the above indexes were significantly different in model group(all P<0.01);compared with model group,the above indexes were significantly different in experimental-L,experimental-M,experimental-H groups and positive control group(all P<0.01).Conclusionω-3 PUFA can ameliorate chronic atrophic gastritis of rats,and the mechanism may be related to the anti-inflammatory,anti-apoptosis and anti-oxidative stress effects of to-3 PUFA.
7.Molecular epidemiological analysis of plague at the border area of Yunnan Province
Feng-Yi YANG ; Rong YANG ; Si-Ru LI ; Jin-Jiao KONG ; Hong-Li TAN ; Hai-Peng ZHANG ; Peng WANG ; You-Hong ZHONG ; Li-Yuan SHI ; Zhi-Zhong SONG
Chinese Journal of Zoonoses 2024;40(5):401-407
This study was aimed at exploring the epidemiological characteristics of plague,and the evolutionary relation-ships among the isolated plague strains in the Yunnan border area,to provide clues for further studying epidemic causes and ep-idemiological patterns.Plague epidemic data in the border area during the second epidemic period(1982-2007)were collected and analyzed with descriptive epidemiological methods.Whole genome sequences of 262 strains of Yersinia pestis in the border area were obtained for phylogenetic analysis.Plague outbreaks occurred in 17 counties(cities)among 25 border counties(cit-ies);a total of 552 epidemic foci and 123 human cases were identified.The 1.ORI2,1.ORI3,1.IN3,2.ANT and 2.MED geno-types were identified among Yersinia pestis isolated from the Yunnan border area,among which the 1.ORI2 population was dominant.A total of 258 strains of Yersinia pestis from the 1.OR12 population belonged to four subclusters.The Myanmar and Vietnam clade was embedded within the Yunnan clade in the overall phylogeny.The above results indicated that during the sec-ond period of the epidemic,the intensity of plague epidemics in Yunnan's border areas was high,showing a trend of devel-opment from west to south and east.Our findings indicated a risk of cross-border transmission of plague between Yunnan and neighboring countries;therefore,the surveillance,pre-vention,and control of plague in border areas should be strengthened.
8.Mismatch ratio in CT perfusion and diffusion weighted imaging to evaluate the lesion outcome of acute ischemic stroke patients
Yanjun XIE ; Dequan CHEN ; Jing PENG ; Xingpan YOU ; Yu CAI ; Bin GUAN ; Yuan YU ; Lidan YANG
Journal of Practical Radiology 2024;40(7):1043-1047
Objective To investigate the influencing factors of Mismatch ratio in computed tomography perfusion(CTP)and dif-fusion weighted imaging(DWI)to assess the lesion outcome after treatment in patients with acute ischemic stroke(AIS).Methods Whether there were any differences in clinical and imaging data of AIS patients were analyzed retrospectively between the Mismatch ratio>1.2 group and the Mismatch ratio≤1.2 group,and between the hemorrhagic transformation group and the non-hemorrhagic transformation group.Results The age of onset and National Institutes of Health Stroke Scale(NIHSS)score of AIS patients in the group with Mismatch ratio>1.2 were greater than those in the group with Mismatch ratio≤1.2.The Mismatch ratio>1.2 group had lower incidence of hyperlipidemia,new infarct foci,and higher hypercoagulability,cerebral hemorrhage,as well as large cerebral infarction.The NIHSS score was higher in the hemorrhagic transformation group than the non-hemorrhagic transformation group,and the incidence of large cerebral infarction and digital subtraction angiography(DSA)thrombectomy was higher in the former than in the latter.Multifactorial logistic analysis showed that age,NIHSS score,and hyperlipidemia were independent risk factors for AIS patients with Mismatch ratio>1.2 and large cerebral infarction was an independent risk factor for hemorrhagic transformation.Conclusion The Mismatch ratio in CTP is correlated with age,NIHSS score,and hyperlipidemia in patients with AIS and large cerebral infarction is correlated with hemorrhagic transformation.
9.Rigid-body inverse dynamics modelling and analysis of 6RSS parallel bio-inspired masticatory robot
Chen CHENG ; Xiao-Jing YUAN ; Neng-Jun YANG ; Gen-Liang HOU ; Fan-Qi ZENG ; You-Cai WANG ; Wei-Peng LUO ; Guan ZHAO
Chinese Medical Equipment Journal 2024;45(3):16-22
Objective To carry out rigid-body inverse dynamics modelling and analysis of a self-designed 6RSS parallel bio-inspired masticatory robot.Methods Firstly,the functions of kinematic variables including translational/rotational velocities and accelerations were derived for rigid-body inverse dynamics modelling.Secondly,the rigid-body inverse dynamics model was established with the Newton-Euler's law.Finally,the chewing motion trajectories of the oral health volunteers were tracked and numerical calculations were carried out in the case where the robot was subjected to a chewing reaction force.Results Numerical calculations showed that the driving torque and the constraint force of the robot peaked when the chewing reaction force was at its maximum.Conclusion The external force has a large impact on the inverse dynamics of the robot,and theoretical references are provided for the motion control and optimal design of the robot.[Chinese Medical Equipment Journal,2024,45(3):16-22]
10.Application of "eliminating stagnation and bloodletting/fire needling" in treatment of jingjin diseases.
Jun YANG ; Hui-Lin LIU ; Bin LI ; Ying CHANG ; Lu LIU ; Peng CHEN ; Wei YOU ; Shao-Song WANG ; Fan ZHANG ; Yuan-Bo FU ; Jia WEI
Chinese Acupuncture & Moxibustion 2023;43(8):889-893
Based on the development of conditions, the etiology and pathogenesis of jingjin (muscle region of meridian) diseases are summarized as 3 stages, i.e. stagnation due to over-exertion at early stage, manifested by tendon-muscle contracture and tenderness; cold condition due to stagnation, interaction of stasis and cold, resulting in clustered nodules at the middle stage; prolonged illness and missed/delayed treatment, leading to tendon-muscle contracture and impairment of joint function at the late stage. It is proposed that the treatment of jingjin diseases should be combined with the characteristic advantages of fire needling and bloodletting technique, on the base of "eliminating stagnation and bloodletting/fire needling". This combined therapy warming yang to resolve stasis and dispels cold to remove nodules, in which, eliminating the stagnation is conductive to the tissue regeneration, and the staging treatment is delivered in terms of the condition development at different phases.
Acupuncture Therapy/methods*
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Bloodletting
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Medicine, Chinese Traditional
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Muscular Diseases/therapy*
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Humans
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Hot Temperature/therapeutic use*
;
Contracture/therapy*

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