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.

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 discuss the effect of microRNA(miR)-30c-5p on the proliferation,migration,and invasion of the human prostate cancer cells(LNCap),and to clarify its possible mechanism.Methods:The LNCap cells were divided into LNCap group(without plasmid transfection),miR-30c-5p mimic group(transfected with miR-30c-5p mimic),mimic NC group(transfected with miR-30c-5p mimic NC),sh-DNA damage inducible transcript 4(DDIT4)group(transfected with sh-DDIT4),sh-NC group(transfected with sh-DDIT4 NC),miR-30c-5p mimic+pc-DNA3.1-NC group(co-transfected with miR-30c-5p mimic and pc-DNA3.1 empty vector),and miR-30c-5p mimic+pc-DNA3.1-DDIT4 group(co-transfected with miR-30c-5p mimic and pc-DNA3.1-DDIT4 over-expression plasmid).The RWPE-1 cells were cultured normally.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-30c-5p and DDIT4 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of DDIT4 protein in the cells in various groups;CCK-8 method was used to detect the proliferation rates of the LNCap cells in various groups;Transwell assay was used to detect the numbers of the invasion LNCap cells in various groups;Scratch assay was used to detect the scratch healing rates of LNCap cells in various groups;dual-luciferase reporter assay was used to detect the targeting relationship between miR-30c-5p and DDIT4.In the in vivo tumor formation experiment,18 male BALB/c nude mice were divided randomly into blank group,agomiR-NC group(transfected with agomiR-30c-5p NC),and agomiR-30c-5p group(transfected with agomiR-30c-5p);there were six mice in each group.The mice in agomiR-NC group and agomiR-30c-5p group were subcutaneously injected with LNCap cells,while the mice in blank group were given an equal volume of physiological saline.The volumes of tumor of the mice in various groups were detected.HE staining was used to observe the morphology of prostate cancer tissue the mice of in various groups;RT-qPCR method and immunofluorescence staining were used to detect the expression levels of miR-30c-5p and DDIT4 mRNA and the fluorescence intensities of DDIT4 protein in prostate cancer tissue of the mice in various groups.Results:The In vitro prostate cancer cell experiment results showed that compared with RWPE-1 cells,the expression level of miR-30c-5p in the prostate cancer LNCap cells was decreased(P<0.01),and the expression levels of DDIT4 mRNA and protein were increased(P<0.05 or P<0.01).After 48 of transfection,compared with LNCap group and mimic NC group,the expression level of miR-30c-5p in the LNCap cells in miR-30c-5p mimic group was increased(P<0.01).Compared with LNCap group and sh-NC group,the expression level of DDIT4 mRNA in the LNCap cells in sh-DDIT4 group was decreased(P<0.01).Compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the expression level of miR-30c-5p in The LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was decreased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the expression level of DDIT4 mRNA in the LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the expression level of DDIT4 protein in the LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.05).The CCK-8 method results showed that compared with LNCap group and mimic NC group,the proliferation rate of the LNCap cells in miR-30c-5p mimic group was decreased(P<0.01);compared with LNCap group and sh-NC group,the proliferation rate of the LNCap cells in sh-DDIT4 group was decreased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the proliferation rate of the LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.01).The Transwell assay results showed that compared with LNCap group and mimic NC group,the number of the invasion LNCap cells in miR-30c-5p mimic group was decreased(P<0.01);compared with LNCap group and sh-NC group,the number of invasion LNCap cells in sh-DDIT4 group was decreased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the number of the invasion LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.01).The scratch assay results showed that compared with LNCap group and mimic NC group,the scratch healing rate of the LNCap cells in miR-30c-5p mimic group was decreased(P<0.01);compared with LNCap group and sh-NC group,the scratch healing rate of the LNCap cells in sh-DDIT4 group was decreased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the scratch healing rate of the LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.01).The dual-luciferase reporter assay results showed that compared with the LNCap cells co-transfected with WT-DDIT4 and mimic NC,the luciferase activity of the LNCap cells co-transfected with WT-DDIT4 and miR-30c-5p mimic was decreased(P<0.01).The in vivo nude mouse tumor formation experiment results showed that on the 3 rd,6 th,9 th,12 th,and 15th days after cell injection,compared with blank group and agomiR-NC group,the tumor volumes of the nude mice in agomiR-30c-5p group were decreased(P<0.05).The HE staining results showed that in prostate cancer tissue of the mice in blank group and agomiR-NC group,the cell nuclei were enlarged,and nucleoli were prominent and deformed.In the mice in agomiR-30c-5p group,some regions of prostate cancer tissues results showed neatly arranged cells with normally shaped nuclei.The RT-qPCR and immunofluorescence staining showed that compared with agomiR-NC group,the expression level of miR-30c-5p in prostate cancer tissue of the mice in agomiR-30c-5p group was increased(P<0.01).Compared with blank group and agomiR-NC group,the expression level of DDIT4 mRNA in prostate cancer tissue of the mice in agomiR-30c-5p group was decreased(P<0.01).DDIT4 protein was mainly expressed in the cytoplasm.Compared with blank group and agomiR-NC group,the fluorescence intensity of DDIT4 protein in prostate cancer tissue of the mice in agomiR-30c-5p group was decreased(P<0.01).Conclusion:The expression level of miR-30c-5p in the prostate cancer LNCap cells is decreased,and it inhibits the proliferation,migration,and invasion of the prostate cancer cells by targeting downregulation of DDIT4,thereby participating in the occurrence and development of prostate cancer.

Adrenocortical carcinoma(ACC)is the most prevalent malignant tumor of the adrenal gland and is characterized by a poor pro-gnosis in its advanced stages.Surgical resection of the tumors is typically limited to patients diagnosed in the clinical stages Ⅰ and Ⅱ,lead-ing to a high postoperative recurrence rate.The combination of mitotane(M)with etoposide(E),doxorubicin(D),and cisplatin(P)(EDP-M)is currently the only approved first-line treatment regimen for advanced ACC.However,the efficacy of chemotherapy and radiation therapy in ACC remains limited.If the EDP-M regimen proves ineffective,there are no standardized or universally accepted second-line systemic treat-ment alternatives.Research advancements in the molecular mechanisms of ACC in recent years has led to increasing investigations on tyr-osine kinase inhibitors(TKIs)targeting EGFR,VEGFR,and mTOR,as well as immune checkpoint inhibitors(ICIs).Moreover,previous studies have identified mutations in CTNBB1,TP53,KDM5A,CENP-H,and other genes that may serve as therapeutic targets or biomarkers,thereby expanding the treatment options available for ACC.ICIs are effective against diverse cancer types,including non-small cell lung cancer(NSCLC),liver cancer,renal cell cancer,and urothelial cancer.Ongoing exploration into targeted therapies and immunotherapy,especially combination treatments,holds the promise of extending the survival of patients and enhancing their quality of life.

Objective To investigate the changes of dorsal root ganglia(DRG)neurons in rats with voltage-gated sodium channel 1.7 loss-of-function(Nav1.7 LOF)and its involvement in congenital insensitivity to pain.Methods Immunofluorescence,Western blot,and alternative splicing analysis were used to verify the expression deletion of DRG neurons and Nav1.7 in spinal cord of Nav1.7 LOF rats.Using antibodies for peripherin,calcitonin gene-related peptide(CGRP),isolectin B4(IB4),and neuronal nuclear antigen(NeuN)in the DRG and spinal cord tissues,immunofluorescence staining was performed to observe the differences in DRG neuronal sub-populations and central terminal projections between Nav1.7 LOF rats and wild-type rats.Bulk RNA-Seq and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the difference of gene expression in the DRG neurons between Nav1.7 LOF and WT rats.Following 55℃ thermal stimulation of the hind paw in Nav1.7 LOF rats,c-Fos and phospho-extracellular signal-regulated kinase(p-ERK)antibody staining was used to observe the activation of DRG neurons and spinal dorsal horn neurons.Results Nav1.7 was absent in the DRG neurons and spinal cord of Nav1.7 LOF rats.Compared with wild-type rats,Nav1.7 LOF rats exhibited a decreased proportion of IB4+non-peptidergic neurons in DRG tissues.Additionally,there was a significant loss of central projections of IB4+neurons in the spinal dorsal horn.The RNA-Seq and RT-qPCR results demonstrate that in Nav1.7 LOF rats,the gene expression of Mas-related G protein-coupled receptor(MRGPR),markers for 1B4+non-peptidergic neurons,was downregulat-ed.Compared with WT rats,there was no difference in c-Fos and p-ERK staining in DRG neurons of Nav1.7 LOF rats following ther-mal stimulation of the hindpaw.However,there was no c-Fos or p-ERK staining in spinal dorsal horn neurons,suggesting that the neu-rons were not activated.Conclusion Nav1.7 LOF rats exhibit a decreased proportion of IB4+non-peptideric neurons in DRG tissue and their central terminal projections.Noxious stimuli could activate DRG neurons,but could not activate dorsal horn neurons,suggesting the pain signal is interrupted between the central terminals of DRG neurons and the spinal dorsal horn.

Objective To investigate the changes of dorsal root ganglia(DRG)neurons in rats with voltage-gated sodium channel 1.7 loss-of-function(Nav1.7 LOF)and its involvement in congenital insensitivity to pain.Methods Immunofluorescence,Western blot,and alternative splicing analysis were used to verify the expression deletion of DRG neurons and Nav1.7 in spinal cord of Nav1.7 LOF rats.Using antibodies for peripherin,calcitonin gene-related peptide(CGRP),isolectin B4(IB4),and neuronal nuclear antigen(NeuN)in the DRG and spinal cord tissues,immunofluorescence staining was performed to observe the differences in DRG neuronal sub-populations and central terminal projections between Nav1.7 LOF rats and wild-type rats.Bulk RNA-Seq and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the difference of gene expression in the DRG neurons between Nav1.7 LOF and WT rats.Following 55℃ thermal stimulation of the hind paw in Nav1.7 LOF rats,c-Fos and phospho-extracellular signal-regulated kinase(p-ERK)antibody staining was used to observe the activation of DRG neurons and spinal dorsal horn neurons.Results Nav1.7 was absent in the DRG neurons and spinal cord of Nav1.7 LOF rats.Compared with wild-type rats,Nav1.7 LOF rats exhibited a decreased proportion of IB4+non-peptidergic neurons in DRG tissues.Additionally,there was a significant loss of central projections of IB4+neurons in the spinal dorsal horn.The RNA-Seq and RT-qPCR results demonstrate that in Nav1.7 LOF rats,the gene expression of Mas-related G protein-coupled receptor(MRGPR),markers for 1B4+non-peptidergic neurons,was downregulat-ed.Compared with WT rats,there was no difference in c-Fos and p-ERK staining in DRG neurons of Nav1.7 LOF rats following ther-mal stimulation of the hindpaw.However,there was no c-Fos or p-ERK staining in spinal dorsal horn neurons,suggesting that the neu-rons were not activated.Conclusion Nav1.7 LOF rats exhibit a decreased proportion of IB4+non-peptideric neurons in DRG tissue and their central terminal projections.Noxious stimuli could activate DRG neurons,but could not activate dorsal horn neurons,suggesting the pain signal is interrupted between the central terminals of DRG neurons and the spinal dorsal horn.

Carotid atherosclerosis (CAS) is closely associated with the decline of cognitive function in the elderly, which can lead to persistent or progressive cognitive function and neurological dysfunction. Vascular cognitive impairment (VCI) is considered to be an intervenable disease. Studies have shown that CAS is one of the main causes of VCI. Further study on the relationship between CAS and VCI will help to better prevention and treatment of VCI.

Vascular cognitive impairment (VCI) is the second most common type of dementia after Alzheimer's disease. As the pathway between the central nervous system and gastrointestinal tract, brain-gut axis has become one of the research hotspots in the pathogenesis of many diseases. Intestinal flora imbalance may mediate or affect vascular risk factors such as atherosclerosis, hypertension, metabolic diseases, and ischemic stroke, and finally accelerate the occurrence and development of VCI. This article reviews the literature on intestinal flora and VCI as well as its main risk factors, in order to provide new ideas for the prevention and treatment of VCI.

Neutrophil to lymphocyte ratio (NLR) can provide information of local or systemic inflammation and immune status. With the increasing attention to the role of inflammatory and immune factors in vascular cognitive impairment (VCI), it is very important to find new serum inflammatory markers for early identification and intervention of VCI. This article reviews the related research on NLR, VCI and their risk factors, expounds the role of inflammation in the pathogenesis of VCI, and provides help for the diagnosis and prevention of VCI.