1.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: A resting-state functional magnetic resonance imaging study.
Xuan YIN ; Xiao-Ling ZENG ; Jing-Jing LIN ; Wen-Qing XU ; Kai-Yu CUI ; Xiu-Tian GUO ; Wei LI ; Shi-Fen XU
Journal of Integrative Medicine 2025;23(2):159-168
OBJECTIVE:
Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA.
METHODS:
Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment.
RESULTS:
Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex.
CONCLUSION
EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals
;
Electroacupuncture
;
Male
;
Magnetic Resonance Imaging
;
Depression/diagnostic imaging*
;
Mice, Inbred C57BL
;
Brain/diagnostic imaging*
;
Disease Models, Animal
;
Mice
;
Pain/diagnostic imaging*
;
Acupuncture Points
2.Association of Co-Exposure to Polycyclic Aromatic Hydrocarbons and Metal(loid)s with the Risk of Neural Tube Defects: A Case-Control Study in Northern China.
Xiao Qian JIA ; Yuan LI ; Lei JIN ; Lai Lai YAN ; Ya Li ZHANG ; Ju Fen LIU ; Le ZHANG ; Linlin WANG ; Ai Guo REN ; Zhi Wen LI
Biomedical and Environmental Sciences 2025;38(2):154-166
OBJECTIVE:
Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD.
METHODS:
Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with 32P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects.
RESULTS:
In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs.
CONCLUSION
Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans
;
Neural Tube Defects/chemically induced*
;
Polycyclic Aromatic Hydrocarbons/adverse effects*
;
Female
;
Case-Control Studies
;
China/epidemiology*
;
Adult
;
Pregnancy
;
Environmental Pollutants
;
Maternal Exposure/adverse effects*
;
Metals/toxicity*
;
Young Adult
;
Risk Factors
3.Association between short-term exposure to meteorological factors on hospital admissions for hemorrhagic stroke: an individual-level, case-crossover study in Ganzhou, China.
Kailun PAN ; Fen LIN ; Kai HUANG ; Songbing ZENG ; Mingwei GUO ; Jie CAO ; Haifa DONG ; Jianing WEI ; Qiujiang XI
Environmental Health and Preventive Medicine 2025;30():12-12
BACKGROUND:
Hemorrhagic stroke (HS) is associated with significant disability and mortality. However, the relationship between meteorological factors and hemorrhagic stroke, as well as the potential moderating role of these factors, remains unclear.
METHODS:
Daily data on HS, air pollution, and meteorological conditions were collected from January 2015 to December 2021 in Ganzhou to analyze the relationship between meteorological factors and HS admissions. This analysis employed a time-stratified case-crossover design in conjunction with a distributional lag nonlinear model. Additionally, a bivariate response surface modelling was utilized to further investigate the interaction between meteorological factors and particulate matter. The study also stratified the analyses by gender and age. To investigate the potential impact of extreme weather conditions on HS, this study defined the 97.5th percentile as representing extremely high weather conditions, while the 2.5th percentile was classified as extremely low.
RESULTS:
In single-day lags, the risk of admissions for HS was significantly associated with extremely low temperature (lag 1-2 and lag 13-14), extremely low humidity (lag 1 and lag 9-12), and extremely high precipitation (lag 2-7). Females exhibited greater susceptibility to extremely low temperature than males within the single-day lag pattern in the subcomponent layer, with a maximum relative risk (RR) that was 7% higher. In the cumulative lag analysis, the risk of HS admissions was significantly associated with extremely high temperature (lag 0-8∼lag 0-14), extremely low humidity (lag 0-2∼lag 0-14), and extremely high precipitation (lag 0-4∼lag 0-14). Within the cumulative lag day structure of the subcomponent layer, both extremely low and extremely high temperature had a more pronounced effect on females and aged ≥65 years. The risk of HS admissions was positively associated with extremely high barometric pressure in the female subgroups (lag 0-1 and lag 0-2). The highest number of HS admissions occurred when high PM2.5 concentrations coexisted with low precipitation.
CONCLUSIONS
Meteorological factors were significantly associated with the risk of hospital admissions for HS. Individuals who were female and aged ≥65 years were found to be more susceptible to these meteorological influences. Additionally, an interaction was observed between airborne particulate matter and meteorological factors. These findings contributed new evidence to the association between meteorological factors and HS.
China/epidemiology*
;
Humans
;
Female
;
Male
;
Aged
;
Middle Aged
;
Cross-Over Studies
;
Hospitalization/statistics & numerical data*
;
Adult
;
Hemorrhagic Stroke/etiology*
;
Meteorological Concepts
;
Weather
;
Particulate Matter/analysis*
;
Air Pollution/adverse effects*
;
Environmental Exposure/adverse effects*
;
Aged, 80 and over
;
Young Adult
4.Astragaloside IV Alleviates Podocyte Injury in Diabetic Nephropathy through Regulating IRE-1α/NF-κ B/NLRP3 Pathway.
Da-Lin SUN ; Zi-Yi GUO ; Wen-Yuan LIU ; Lin ZHANG ; Zi-Yuan ZHANG ; Ya-Ling HU ; Su-Fen LI ; Ming-Yu ZHANG ; Guang ZHANG ; Jin-Jing WANG ; Jing-Ai FANG
Chinese journal of integrative medicine 2025;31(5):422-433
OBJECTIVE:
To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism.
METHODS:
In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively.
RESULTS:
Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis.
CONCLUSION
AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism*
;
Animals
;
Diabetic Nephropathies/metabolism*
;
Saponins/therapeutic use*
;
Triterpenes/therapeutic use*
;
Signal Transduction/drug effects*
;
NF-kappa B/metabolism*
;
Protein Serine-Threonine Kinases/metabolism*
;
Male
;
Rats, Sprague-Dawley
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Endoribonucleases/metabolism*
;
Endoplasmic Reticulum Chaperone BiP
;
Rats
;
Diabetes Mellitus, Experimental/complications*
;
Endoplasmic Reticulum/metabolism*
;
Multienzyme Complexes
5.Hysteresis displacement control of piezoceramics based on improved Bouc-Wen model
Yuan-yuan CHAI ; Wei-guo WANG ; Xiao-fen LIU ; Liang-yu CUI
Chinese Medical Equipment Journal 2025;46(8):25-31
Objective To propose an improved Bouc-Wen model to alleviate the nonlinear effect of the hysteresis displacement of piezoceramics and enhance the motion control accuracy of the nano-displacement platform.Methods Firstly,two fine-tuning parameters including the asymmetric term and the input bias term were added to the classical Bouc-Wen model to eliminate the deviation of the starting and ending positions of the hysteresis curve,so as to obtain an improved Bouc-Wen model simulating the hysteresis displacement characteristics of piezoceramics on the nano-displacement platform.Secondly,the parameters of the improved Bouc-Wen model were identified based on the particle swarm optimization algorithm,and an inverse feedforward structure was adopted to realize the linearized control of the output displacement.Finally,an experimental system was built to verify the linearized control effect of the improved Bouc-Wen model.Results The hysteresis curve of the improved Bouc-Wen model fitted the actual voltage-displacement curve of piezoceramics significantly better when compared with that of the traditional model,which had a 56%reduction in the fitting error and a 0.03 μm error between the desired and actual displacements during the linearized output control with a driving voltage of 0-60 V and a maximum travel of about 4 μm.Conclusion The improved Bouc-Wen model behaves well in hysteresis displacement fitting and linearized output control,and a new idea is provided for enhancing the motion control accuracy of the nano-displacement platform.[Chinese Medical Equipment Journal,2025,46(8):25-31]
6.Protective mechanism of sevoflurane on acute lung injury in sepsis by regulating the Wnt/β-catenin signal-ing pathway
Jinyan GUO ; Yuqing YOU ; Ke CHEN ; Fen PAN ; Jiahui LAI ; Sufang CHEN ; Weifeng YAO
The Journal of Practical Medicine 2025;41(19):2991-2999
Objective To explore the role of sevoflurane(SEV)in sepsis-induced acute lung injury(ALI)and observe its impact on the Wnt/β-catenin signaling pathway.Methods Forty C57 mice were randomly divided into 4 groups(n=10 each):Sham,CLP,SEV,and SEV+XAV(β-catenin inhibitor).A sepsis model was established via cecal ligation and puncture.Lung injury was evaluated using HE staining,lung wet/dry weight ratio,and TUNEL staining.Levels of inflammatory factors(TNF-α,IL-1β,IL-6)were detected by ELISA.Oxidative stress indices(SOD,MDA,ROS)were measured by colorimetry and flow cytometry.Hindlimb blood perfusion and oxygenation were assessed with laser speckle flowmetry.Expressions of key Wnt pathway molecules and down-stream target genes(c-Myc,Cyclin D1)were detected by RT-qPCR and Western blot.Co-localization of β-catenin and SP-C(a marker of type Ⅱ alveolar epithelial cells)in lung tissues was determined by immunofluorescence staining.Results Compared with the Sham group,the CLP group exhibited significant increases in sepsis severity,lung pathological damage including alveolar structure destruction,inflammatory infiltration,and apoptosis,elevation in pro-inflammatory cytokine levels,and significant decrease in SOD and increase in MDA and ROS.Additionally,lower limb blood flow and oxygenation levels were significantly reduced,while the expression of β-catenin and its downstream target genes,as well as the co-localization signal and fluorescence intensity of β-catenin with SP-C,were significantly downregulated(all P<0.05).Compared with the CLP group,the SEV group showed significant improvements in all these indicators.However,compared with the SEV group,the SEV+XAV group demon-strated a reversed protective effect,with all indicators approaching the levels observed in the CLP group(all P<0.05).Conclusion Sevoflurane alleviates sepsis-induced ALI by activating Wnt/β-catenin signaling pathway,exerting anti-inflammatory and antioxidant effects,and enhancing the expression and localization of β-catenin in type Ⅱ alveolar epithelial cells.
7.Quantitative evaluation of left ventricular remodeling in left bundle branch block induced cardiomyopathy by multimodal imaging
Xiaoxian WANG ; Changqing MIAO ; Beibei GE ; Mingxia LI ; Fen CHEN ; Fang XU ; Ning ZHANG ; Guanjun GUO ; Wei XU ; Wenzhi SHEN ; Yingming ZHAO ; Jing YAO
Chinese Journal of Ultrasonography 2025;34(1):26-32
Objective:To quantitatively evaluate the effects of left bundle branch block(LBBB)on left ventricular structure,function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography(SPECT),and to investigate the relationship between myocardial work,myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy(LBBB-CM).Methods:Fourteen male beagle dogs were selected,and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram(ECG),transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs(normal control group)matched by age and weight. The correlation between myocardial perfusion(percentage of regional tracer uptake)and myocardial work parameters,myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline,the left ventricular end-diastolic volume of 12 months after the ablation increased[(20.78 ± 5.32)ml vs(26.71 ± 7.94)ml, P = 0.003],left ventricular ejection fraction decreased[(59.17 ± 5.67)% vs(47.69 ± 5.45)%, P<0.001];left ventricular global/segmental longitudinal strain,global/segmental constructive work and global/segmental work efficiency decreased(all P<0.05),left ventricular global/segmental wasted work increased(all P<0.001). Heterogenous perfusion defect was observed in LBBB dogs by SPECT,compared with lateral wall segments,the percentage of regional tracer uptake of septum was decreased(all P<0.05). Gross anatomical and myocardial pathological changes were manifested as cardiomegaly,flaky or focal grayish thickening of endocardium,cardiomyocyte degeneration and fibrosis. Compared with normal control group,the collagen fiber volume fraction(CVF)in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased(all P<0.05). Percentage of regional tracer uptake was positively correlated with segmental myocardial work(SMW)and segmental myocardial efficiency(SWE)( r s = 0.49,0.31;both P<0.001),and negatively correlated with CVF and segmental wasted work(SWW)( r s = -0.51,-0.49;both P<0.001). Conclusions:Isolated LBBB is not benign,which can result in left ventricular remodeling,decreased cardiac constructive function,abnormal myocardial perfusion,endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion,as non-invasive examination,can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.
8.The Mesencephalic Locomotor Region for Locomotion Control
Xing-Chen GUO ; Yan XIE ; Xin-Shuo WEI ; Wen-Fen LI ; Ying-Yu SUN
Progress in Biochemistry and Biophysics 2025;52(7):1804-1816
Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.
9.Quantitative evaluation of left ventricular remodeling in left bundle branch block induced cardiomyopathy by multimodal imaging
Xiaoxian WANG ; Changqing MIAO ; Beibei GE ; Mingxia LI ; Fen CHEN ; Fang XU ; Ning ZHANG ; Guanjun GUO ; Wei XU ; Wenzhi SHEN ; Yingming ZHAO ; Jing YAO
Chinese Journal of Ultrasonography 2025;34(1):26-32
Objective:To quantitatively evaluate the effects of left bundle branch block(LBBB)on left ventricular structure,function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography(SPECT),and to investigate the relationship between myocardial work,myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy(LBBB-CM).Methods:Fourteen male beagle dogs were selected,and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram(ECG),transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs(normal control group)matched by age and weight. The correlation between myocardial perfusion(percentage of regional tracer uptake)and myocardial work parameters,myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline,the left ventricular end-diastolic volume of 12 months after the ablation increased[(20.78 ± 5.32)ml vs(26.71 ± 7.94)ml, P = 0.003],left ventricular ejection fraction decreased[(59.17 ± 5.67)% vs(47.69 ± 5.45)%, P<0.001];left ventricular global/segmental longitudinal strain,global/segmental constructive work and global/segmental work efficiency decreased(all P<0.05),left ventricular global/segmental wasted work increased(all P<0.001). Heterogenous perfusion defect was observed in LBBB dogs by SPECT,compared with lateral wall segments,the percentage of regional tracer uptake of septum was decreased(all P<0.05). Gross anatomical and myocardial pathological changes were manifested as cardiomegaly,flaky or focal grayish thickening of endocardium,cardiomyocyte degeneration and fibrosis. Compared with normal control group,the collagen fiber volume fraction(CVF)in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased(all P<0.05). Percentage of regional tracer uptake was positively correlated with segmental myocardial work(SMW)and segmental myocardial efficiency(SWE)( r s = 0.49,0.31;both P<0.001),and negatively correlated with CVF and segmental wasted work(SWW)( r s = -0.51,-0.49;both P<0.001). Conclusions:Isolated LBBB is not benign,which can result in left ventricular remodeling,decreased cardiac constructive function,abnormal myocardial perfusion,endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion,as non-invasive examination,can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.
10.Up-regulation of miR-338-3p alleviates IL-13-induced injury of human bronchial cell line BEAS-2B
Haiwei FU ; Weiwei GUO ; Fen SHENG ; Donghong LIU
Basic & Clinical Medicine 2025;45(3):346-353
Objective To investigate the effects of miR-338-3p on interleukin(IL)-13-induced human bronchial epithelial cell line(BEAS-2B)injury and airway inflammation in mice with ovalbumin(OVA)-induced asthma.Methods OVA was used to replicate an asthma model of mice,which were divided into control group,model group,miR-NC agomir and miR-338-3p agomir intervention groups.HE staining microscopy was employed to ob-serve the pathological morphology of lung tissue,while TUNEL staining was used to assess cell apoptosis in lung tis-sue.ELISA was conducted to measure the levels of interleukin-1β(IL-1β)and tumor necrosis factor(TNF)-α in lung tissue.The BEAS-2B cells were subjected to IL-13-induced injury and divided into control group,IL-13 group,IL-13+miR-NC group,and IL-13+miR-338-3p mimic group.Cell viability was assessed with MTT assay.Flow cytometry was employed to evaluate cell apoptosis.The level of IL-1β and TNF-α in cells was measured by ELISA.The targeting relationship between miR-338-3p and Ras homologous(Rho)was investigated using bioinfor-matics analysis,luciferase assay,Western blot,and functional repair assay.Results Compared to the model group,the miR-338-3p agamid intervention group exhibited a significant reduction in inflammatory cell infiltration and airway wall thickening in lung tissue,as well as decreased cell apoptosis and the level of IL-1β and TNF-α in lung tissue(P<0.05).Compared to the control group,cell viability of BEAS-2B cells in the IL-13+miR-338-3p mimic group exhibited a significant increase(P<0.05),while apoptosis and level of IL-1β and TNF-α within the cells demonstrated a notable decrease(P<0.05).Rho was a target gene of miR-338-3p,and over-expression of Rho attenuated the effect of miR-338-3p mimic on IL-13-induced injury and inflammation in BEAS-2B cells.Conclusions Up-regulation of miR-338-3p can inhibit asthma-related airway inflammation and injury of lung epi-thelial cells with a potential mechanism targeting at Rho gene.

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