Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Ground-breaking advances have been made in systemic therapy for hepatocellular carcinoma(HCC),which have significantly improved the clinical prognosis of patients with advanced HCC.This article summarizes the key advances and clinical challenges in systemic therapy for HCC.With the combination of various novel targeted therapy and immunotherapy regimens and the application of dual immunotherapy regimens,there has been an increasing number of clinical treatment options,while there are still key challenges such as optimization of treatment regimens,management of drug resistance,and treatment of special populations.Current studies are exploring precise classification based on multi-omics characteristics and the strategies for novel combined therapies,and in particular,triple-combination regimens have the potential to break through the bottleneck in efficacy.In the future,it is necessary to establish a more individualized and refined whole-course management system and further improve the long-term survival benefits of patients by optimizing immune microenvironment modulation and transforming therapeutic paradigms.Advances in this field will promote the transition from traditional paradigm to precision medicine in the treatment of HCC.

Objective To investigate the effects of different contrast injection schemes on the image quality of triple-rule-out com-puted tomography angiography(TRO-CTA).Methods A total of 691 patients with acute chest pain who underwent TRO-CTA exami-nation from multiple centers were prospectively selected and randomly divided into mixed group and unmixed group according to dif-ferent contrast injection methods.The image quality of aorta,pulmonary artery and coronary artery in the two groups was evaluated subjectively and objectively and the radiation dose was calculated.Results There were no significant differences in subjective image quality scores,aorta and coronary CT values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)between the two groups(P>0.05),while there were significant differences in pulmo-nary CT values,SNR,CNR and radiation dose between the two groups(P<0.05).Conclusion The utilization of a mixed contrast injection scheme in TRO-CTA can satisfy diagnostic require-ments while ensuring a low proportional dosage and reduced radiation dose,which has clinical application value.

Objective:To explore the expression and ultrastructure distribution of cofilin and its potential mecha-nisms in postsynaptic mitochondrial anchoring and synaptic plasticity in the pre-B?tzinger complex(pre-B?tC)in rats.Methods:Using neurokinin 1 receptor(NK1R)as a morphological marker of the pre-B?tC,we examined the expres-sion and ultrastructure distribution of cofilin in pre-B?tC neurons of normoxic(NOR)and acute intermittent hypoxic(AIH)rats by combining Western blot,RT-qPCR,immunofluorescence,and immunoelectron microscopy.Results:Cofilin was expressed in the nuclei,somata and dendrites of NK1R-positive neurons in the pre-B?tC and its expression decreased after AIH intervention in this region detected.The results of immunoelectron microscopy showed that cofilin was expressed in the dendritic spines and postsynaptic filamentous or flocculent structures of pre-B?tC neurons.A total of 317 synapses were detected in pre-B?tC(NOR:122;AIH:195).In the NOR group,65.6％of the postsynaptic had cofilin expression,while in the AIH group,the proportion decreased to 47.2％.Combining with the role of cofilin in the regulation of actin severing,it is suggested that the severing effect of cofilin on postsynaptic actin is weakened af-ter AIH intervention,which may further enhance the postsynaptic mitochondrial anchoring.Conclusion:Cofilin,an ac-tin binding protein,plays a crucial role in regulating shearing and depolymerization of actin.Decreased cofilin expres-sion induced by AIH suggests an enhanced actin polymerization,which may be involved in the postsynaptic anchoring of mitochondria and the regulation of synaptic plasticity in the pre-B?tC.

Ground-breaking advances have been made in systemic therapy for hepatocellular carcinoma(HCC),which have significantly improved the clinical prognosis of patients with advanced HCC.This article summarizes the key advances and clinical challenges in systemic therapy for HCC.With the combination of various novel targeted therapy and immunotherapy regimens and the application of dual immunotherapy regimens,there has been an increasing number of clinical treatment options,while there are still key challenges such as optimization of treatment regimens,management of drug resistance,and treatment of special populations.Current studies are exploring precise classification based on multi-omics characteristics and the strategies for novel combined therapies,and in particular,triple-combination regimens have the potential to break through the bottleneck in efficacy.In the future,it is necessary to establish a more individualized and refined whole-course management system and further improve the long-term survival benefits of patients by optimizing immune microenvironment modulation and transforming therapeutic paradigms.Advances in this field will promote the transition from traditional paradigm to precision medicine in the treatment of HCC.

Objective:To explore the expression and ultrastructure distribution of cofilin and its potential mecha-nisms in postsynaptic mitochondrial anchoring and synaptic plasticity in the pre-B?tzinger complex(pre-B?tC)in rats.Methods:Using neurokinin 1 receptor(NK1R)as a morphological marker of the pre-B?tC,we examined the expres-sion and ultrastructure distribution of cofilin in pre-B?tC neurons of normoxic(NOR)and acute intermittent hypoxic(AIH)rats by combining Western blot,RT-qPCR,immunofluorescence,and immunoelectron microscopy.Results:Cofilin was expressed in the nuclei,somata and dendrites of NK1R-positive neurons in the pre-B?tC and its expression decreased after AIH intervention in this region detected.The results of immunoelectron microscopy showed that cofilin was expressed in the dendritic spines and postsynaptic filamentous or flocculent structures of pre-B?tC neurons.A total of 317 synapses were detected in pre-B?tC(NOR:122;AIH:195).In the NOR group,65.6％of the postsynaptic had cofilin expression,while in the AIH group,the proportion decreased to 47.2％.Combining with the role of cofilin in the regulation of actin severing,it is suggested that the severing effect of cofilin on postsynaptic actin is weakened af-ter AIH intervention,which may further enhance the postsynaptic mitochondrial anchoring.Conclusion:Cofilin,an ac-tin binding protein,plays a crucial role in regulating shearing and depolymerization of actin.Decreased cofilin expres-sion induced by AIH suggests an enhanced actin polymerization,which may be involved in the postsynaptic anchoring of mitochondria and the regulation of synaptic plasticity in the pre-B?tC.

Objective To investigate the effects of different contrast injection schemes on the image quality of triple-rule-out com-puted tomography angiography(TRO-CTA).Methods A total of 691 patients with acute chest pain who underwent TRO-CTA exami-nation from multiple centers were prospectively selected and randomly divided into mixed group and unmixed group according to dif-ferent contrast injection methods.The image quality of aorta,pulmonary artery and coronary artery in the two groups was evaluated subjectively and objectively and the radiation dose was calculated.Results There were no significant differences in subjective image quality scores,aorta and coronary CT values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)between the two groups(P>0.05),while there were significant differences in pulmo-nary CT values,SNR,CNR and radiation dose between the two groups(P<0.05).Conclusion The utilization of a mixed contrast injection scheme in TRO-CTA can satisfy diagnostic require-ments while ensuring a low proportional dosage and reduced radiation dose,which has clinical application value.

Objective:To detect itching,anxiety,depression behaviors in chronic itch models of mice and observe the activation of γ-aminobutiric acid(GABA)neurons in the ventral sector of the zona incerta(ZIv),and provide mor-phological evidence for their involvement in the modulation of itch information.Methods:Diphenylcyclopropenone(DCP)was used in glutamic acid decarboxylase 67-green fluorescent protein(GAD67-GFP)knock-in mice to establish chronic itch model.Itch behaviors were detected by video tracking system to verify whether the models were successfully established.The anxiety,depression behaviors of chronic itch model mice were detected by using elevated plus maze test(EPM)and tail suspention test(TST).By using GAD67-GFP mice,the distribution of GABAergic neurons in va-rious sectors of the zona incerta(ZI)was observed.And combined with immunofluorescence staining method,double labeling of GABAergic neurons with FOS in ZIv were observed respectively in control and DCP group mice.Results:In brain slices of GAD67-GFP mice,GABAergic neurons can be observed within all sectors of ZI and are more concentrat-ed in ZIv.Compared with control group mice,DCP group mice showed a significant increase in the bouts of scratching(P＜0.001).The time of immobility in TST was significantly higher in DCP group mice than in control group mice,which displayed depression-like behavior.The EPM test showed that the numbers of entries and proportion of time in the cross region in DCP group mice were less than in control group mice.EPM test revealed that DCP group mice exhibited anxiety-like behavior.The results of immunofluorescence staining showed that the number of FOS-positive cells in ZIv was significantly higher in DCP group mice than in control group mice,and abundant co-labeled neurons of FOS and GABAergic neurons were observed in ZIv.Conclusion:GABAergic neurons were predominantly distributed in ZI,and were more concentrated in ZIv.The activation of GABAergic neurons in ZIv of DCP group mice provides morphological evidence on the involvement of GABAergic neurons in chronic itch and associated negative emotions.