The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

ObjectiveTo investigate the mechanism of Huazhuo Jiedu prescription in treating ulcerative colitis （UC） by regulating mitophagy. MethodsThe genes related to mitophagy and UC were retrieved from GeneCards， and then the common genes of mitophagy and UC were analyzed by metascape to identify the genes related to mitophagy in UC. Animal experiments were carried out to decipher the mechanism by which Huazhuo Jiedu prescription treated UC by regulating mitophagy. Sixty C57BL/6 male mice were randomized into normal， model， high-， medium-， and low-dose （50， 25， 12.5 g·kg^-1， respectively） Huazhuo Jiedu prescription， and mesalazine （0.52 g·kg^-1·d^-1） groups， with 10 mice in each group. After successful modeling by the dextran sulfate sodium-free drinking method， the colonic mucosal damage was observed by hematoxylin-eosin staining， and the ultracellular structure of colon mucosa was observed by transmission electron microscopy. The expression levels of mitophagy-related proteins PTEN-induced putative kinase 1 （PINK1） and Parkin protein were determined by Western blot. The expression of prohibitin 2 （PHB2）， ubiquitin-specific protease 15 （USP15）， ubiquitin-specific protease 30 （USP30） in the colon tissue was detected by immunofluorescence （IF）. ResultsAll the drug intervention groups showed ameliorated pathological manifestations of the colonic mucosa and improved mitochondrial structures in UC mice. Compared with the normal group， the model group demonstrated up-regulated protein levels of PINK1 and Parkin （P<0.05）， enhanced average fluorescence intensity of PHB2 （P<0.05）， and weakened average fluorescence intensity of USP15 and USP30 （P<0.05）. Compared with the model group， the mesalazine group and the high- and medium-dose Huazhuo Jiedu prescription groups showcased down-regulated protein levels of PINK1 and Parkin （P<0.05）， decreased average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. The low-dose Huazhuo Jiedu prescription group showed down-regulated protein levels of PINK1 and Parkin （P<0.05）， weakened average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. ConclusionHuazhuo Jiedu prescription can attenuate the intestinal mucosal injury and improve the mitochondrial cell ultrastructure in UC mice by regulating the expression of PINK1-Parkin pathway and inhibiting excessive mitophagy.

ObjectiveTo investigate the mechanism of Huazhuo Jiedu prescription in treating ulcerative colitis （UC） by regulating mitophagy. MethodsThe genes related to mitophagy and UC were retrieved from GeneCards， and then the common genes of mitophagy and UC were analyzed by metascape to identify the genes related to mitophagy in UC. Animal experiments were carried out to decipher the mechanism by which Huazhuo Jiedu prescription treated UC by regulating mitophagy. Sixty C57BL/6 male mice were randomized into normal， model， high-， medium-， and low-dose （50， 25， 12.5 g·kg^-1， respectively） Huazhuo Jiedu prescription， and mesalazine （0.52 g·kg^-1·d^-1） groups， with 10 mice in each group. After successful modeling by the dextran sulfate sodium-free drinking method， the colonic mucosal damage was observed by hematoxylin-eosin staining， and the ultracellular structure of colon mucosa was observed by transmission electron microscopy. The expression levels of mitophagy-related proteins PTEN-induced putative kinase 1 （PINK1） and Parkin protein were determined by Western blot. The expression of prohibitin 2 （PHB2）， ubiquitin-specific protease 15 （USP15）， ubiquitin-specific protease 30 （USP30） in the colon tissue was detected by immunofluorescence （IF）. ResultsAll the drug intervention groups showed ameliorated pathological manifestations of the colonic mucosa and improved mitochondrial structures in UC mice. Compared with the normal group， the model group demonstrated up-regulated protein levels of PINK1 and Parkin （P<0.05）， enhanced average fluorescence intensity of PHB2 （P<0.05）， and weakened average fluorescence intensity of USP15 and USP30 （P<0.05）. Compared with the model group， the mesalazine group and the high- and medium-dose Huazhuo Jiedu prescription groups showcased down-regulated protein levels of PINK1 and Parkin （P<0.05）， decreased average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. The low-dose Huazhuo Jiedu prescription group showed down-regulated protein levels of PINK1 and Parkin （P<0.05）， weakened average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. ConclusionHuazhuo Jiedu prescription can attenuate the intestinal mucosal injury and improve the mitochondrial cell ultrastructure in UC mice by regulating the expression of PINK1-Parkin pathway and inhibiting excessive mitophagy.

Tissue-resident memory T cells(TRM)are a key immune memory cell type responsible for the recurrence of many skin diseases.TRM cells remain in the skin tissue following infection or injury and maintain immune memory by forming a memory reservoir.When the same or similar external stimuli are encountered again,TRM cells can be rapidly activated,releasing inflammatory cytokines and cytotoxic substances,leading to local tissue damage and/or disease recurrence.The formation and function of TRM cells are regulated by various factors,such as T cell receptor signals,cytokines,co-stimulatory molecules,etc.Furthermore,TRM cells may exhibit different phenotypes and functions in different types of skin diseases.Therefore,understanding the characteristics and regulatory mechanisms of TRM cells is of great significance for studying the mechanisms of skin disease recurrence as well as for developing therapeutic strategies targeting TRM cells.

Objective:To summarize the clinical and imaging presentations of the pontine tegmental cap dysplasia (PTCD).Methods:The clinical, high resolution CT(HRCT) and MRI materials of 4 patients with PTCD between August 2007 to December 2024 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 10 months to 16 years.Results:Of 4 PTCD patients, severe or profound severe hearing loss ( n=8 ears), developmental delay, hypotonia and severe facioplegia ( n=3 cases) were found. On HRCT, all of 4 cases were associated with temporal anomalies [including a narrow bony cochlear nerve canal ( n=8 ears), duplicated (each n=4 ears) or narrow ( n=1 ear) internal auditory canal, enlarged vestibular aqueduct ( n=2 ears), enlarged vestibules and dysplastic lateral semicircular canals ( n=3 ears), ossicular deformation( n=2 ears). The stenosis of the labyrinthine segments of the facial nerve canal ( n=3 ears) and facial nerve canal ectopia(n=6 ears)], atrial or ventricular septal defect (each n=1 case), thoracic or lumbar vertebral anomalies and ribs fusion ( n=3 cases). On the brain MRI, the variable flattening of the ventral pons and dysmorphism of the dorsal upper pons cap-like bulging and protruding in the fourth ventricle were shown in all cases, the vermian and cerebellar peduncles hypoplasia gave rise to a molar tooth appearance. The dysplastic ( n=3 ears), aplastic( n=5 ears) cochlear nerves and dysplastic facial nerves ( n=3 ears) were found. Conclusion:The PTCD patients usually present severe hearing loss, developmental delay, hypotonia, and facioplegia. The flattening of the ventral pons and the dorsal upper pons cap-like bulging usually with duplicated internal auditory canal and severe facial and auditory nerves dysplasia are its imaging features.

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

ObjectiveTo explore the therapeutic effect and mechanism of Xianglian Huazhuo prescription on chronic atrophic gastritis （CAG） in rats based on the Hedgehog signaling pathway. MethodsThe CAG rat model was established by sodium salicylate， N-methyl-N′-nitro-N-nitroguanidine （MNNG）， and irregular feeding. The successfully modeled rats were randomly divided into a model group （180 mg·L^-1）， a moradan group （1.4 g·kg^-1）， and Xianglian Huazhuo Prescription groups with high， medium， and low doses （36， 9， 18 g·kg^-1）， followed by drug intervention. Hematoxylin-eosin （HE） staining was used to observe morphological changes in the gastric mucosa. Transmission electron microscopy was used to observe the ultrastructure of gastric mucosa cells. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Sonic Hedgehog （Shh）， Patched 1 （Ptch1）， and Glioma-associated oncogene homolog 1 （Gli1）. Western blot was used to detect the protein expression levels of Shh， Ptch1， and Gli1 in the gastric mucosa. Immunohistochemistry was used to observe the protein expression of the epithelial marker E-cadherin. ResultsCompared with the normal group， the CAG model group showed a reduction in gastric mucosal intrinsic glands and infiltration of inflammatory cells. The ultrastructure of gastric mucosal cells showed nuclear pyknosis， fewer mitochondria， and abnormal mitochondrial structure. The mRNA and protein expression of Shh， Ptch1， and Gli1 in the gastric mucosa were significantly decreased （P<0.05）， and E-cadherin protein expression was decreased. Compared with the model group， the intervention groups showed varying degrees of improvement in histopathological morphology and cellular ultrastructure. The mRNA and protein expression of Shh， Ptch1， Gli1， and E-cadherin increased to varying degrees. Xianglian Huazhuo Prescription upregulated the expression of key Hedgehog pathway factors and E-cadherin at both the mRNA and protein levels （P<0.05）. ConclusionXianglian Huazhuo prescription has a therapeutic effect on CAG in rats， and its mechanism may be related to activation of the Hedgehog signaling pathway and inhibition of epithelial-mesenchymal transition （EMT）.

Tissue-resident memory T cells(TRM)are a key immune memory cell type responsible for the recurrence of many skin diseases.TRM cells remain in the skin tissue following infection or injury and maintain immune memory by forming a memory reservoir.When the same or similar external stimuli are encountered again,TRM cells can be rapidly activated,releasing inflammatory cytokines and cytotoxic substances,leading to local tissue damage and/or disease recurrence.The formation and function of TRM cells are regulated by various factors,such as T cell receptor signals,cytokines,co-stimulatory molecules,etc.Furthermore,TRM cells may exhibit different phenotypes and functions in different types of skin diseases.Therefore,understanding the characteristics and regulatory mechanisms of TRM cells is of great significance for studying the mechanisms of skin disease recurrence as well as for developing therapeutic strategies targeting TRM cells.

Objective:To summarize the clinical and imaging presentations of the pontine tegmental cap dysplasia (PTCD).Methods:The clinical, high resolution CT(HRCT) and MRI materials of 4 patients with PTCD between August 2007 to December 2024 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 10 months to 16 years.Results:Of 4 PTCD patients, severe or profound severe hearing loss ( n=8 ears), developmental delay, hypotonia and severe facioplegia ( n=3 cases) were found. On HRCT, all of 4 cases were associated with temporal anomalies [including a narrow bony cochlear nerve canal ( n=8 ears), duplicated (each n=4 ears) or narrow ( n=1 ear) internal auditory canal, enlarged vestibular aqueduct ( n=2 ears), enlarged vestibules and dysplastic lateral semicircular canals ( n=3 ears), ossicular deformation( n=2 ears). The stenosis of the labyrinthine segments of the facial nerve canal ( n=3 ears) and facial nerve canal ectopia(n=6 ears)], atrial or ventricular septal defect (each n=1 case), thoracic or lumbar vertebral anomalies and ribs fusion ( n=3 cases). On the brain MRI, the variable flattening of the ventral pons and dysmorphism of the dorsal upper pons cap-like bulging and protruding in the fourth ventricle were shown in all cases, the vermian and cerebellar peduncles hypoplasia gave rise to a molar tooth appearance. The dysplastic ( n=3 ears), aplastic( n=5 ears) cochlear nerves and dysplastic facial nerves ( n=3 ears) were found. Conclusion:The PTCD patients usually present severe hearing loss, developmental delay, hypotonia, and facioplegia. The flattening of the ventral pons and the dorsal upper pons cap-like bulging usually with duplicated internal auditory canal and severe facial and auditory nerves dysplasia are its imaging features.

Objective:To summarize the imaging presentations of the fallopian canal cerebrospinal fluid leaking (FCCFL).Methods:The high resolution CT (HRCT)and MRI materials of 4 patients (4 ears) with FCCFL confirmed by surgery between August 2016 to November 2023 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 6 to 69 years.Results:All of the FCCFL were unilateral, including 2 on the left and 2 on the right.Clinically, the patients with FCCFL suffered from clear nasal fluid flow, ear tightness, and hearing loss. On CT, all of the affected ears were depicted markedly dilatation of the proximal portion of fallopian canal(FC), the labyrinthine segment and geniculate fossa were involved in 4 cases, and involvement of tympanic segment in 1 case at the same time. The geniculate fossa in the affected side were significantly enlarged, protruding upwards into the tympanic cavity, with one case simultaneously involving the cochlea. On MRI, the hyposignal on T 1WI and hypersignal on T 2WI or water sequence like cerebrospinal fluid (CSF) were shown in the enlargement FC, without diffusion restriction, and non-enhancing with administration Gadolinium contrast.CSF-like signal effusion was shown in all of the affected tympanum, of which, the CSF-like signal effusion was demonstrated in the area along the superficial petrosal nerve, the right pterygopalatine fossa and the parapharyngeal space. The adjacent intracranial meninges were presented thickening in 3 cases. Conclusion:The imaging appearances of FCCFL present some characteristics:on HRCT, the proximal portions of the affected FC depicts markedly enlargement,especially the geniculate fossa.While they present CSF-like signal, no diffusion restriction, and no enhancement administration, Gadolinium contrast on MRI, accompanying the CSF-like signal effusion in the affected tympanum.