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

Objective:To investigate the effect of estrogen-related receptor α (ESRRA)-mediated lipophagy on the proliferation and migration abilities of nasopharyngeal carcinoma cells.Methods:A total of 16 clinical samples diagnosed by pathology in the Affiliated Hospital of Nantong University from 2021 to 2023 were selected, including 8 normal nasopharyngeal mucosa tissues and 8 nasopharyngeal carcinoma tissues. Immortalized normal nasopharyngeal epithelial cell line NP69 and nasopharyngeal carcinoma cell lines C666-1, CNE2, TW03-EBV and TW03 were selected. The cell lines C666-1 and CNE2 were divided into the siR-NC group (transfected with small interfering RNA negative control sequence) and siR-ESRRA group (transfected with small interfering RNA against ESRRA gene). The relative expression levels of ESRRA were detected by Western blotting and immunohistochemical assay. EdU assay was used to detect the proliferation ability of C666-1 and CNE2 cells, and Transwell assay was used to detect the migration ability. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of ESRRA and perilipin 3 (PLIN3) mRNA. The formation of lipophagy in C666-1 and CNE2 cells was observed by transmission electron microscopy. The co-localization of LC3, PLIN3 and LAMP2 with lipid droplets labeling with Bodipy was detected by immunofluorescence assay. Dual-luciferase reporter gene assay was used to verify the targeting relationship between ESRRA and PLIN3.Results:The relative expression level of ESRRA in nasopharyngeal carcinoma tissues was higher than that in normal nasopharyngeal mucosa tissues(1.15±0.75 vs. 0.32±0.21, t = 3.02, P = 0.009). The relative expression level of ESRRA in nasopharyngeal carcinoma cell lines C666-1 (1.539±0.044), CNE2 (1.420±0.030), TW03-EBV (2.867±0.044), and TW03 (1.323±0.022) were higher than that in normal nasopharyngeal epithelial cell line NP69 (0.094±0.002), and the difference was statistically significant ( F = 34.08, P < 0.001).The results of EdU assay showed that the proportions of EdU labeled positive cells in CNE2 cells of siR-NC group and siR-ESRRA group were (70.44±4.06)% and (51.51±0.92)% ( t = 7.88, P = 0.001), and the proportions in C666-1 cells were (62.25±3.89)% and (54.91±0.27)% ( t = 3.26, P = 0.031). The results of Transwell assay showed that the number of migrating cells in CNE2 and C666-1 cells was less than that in siR-NC group [CNE2 cells: (181±7) cells vs. (261±21) cells; C666-1 cells: (201±16) cells vs. (256±7) cells], and the differences were statistically significant ( t = 6.30, P = 0.003; t = 5.43, P = 0.006). According to qRT-PCR results, the relative expression level of PLIN3 mRNA in the siR-ESRRA group was higher than that in the siR-NC group (CNE2 cells: 1.58±0.16 vs. 0.83±0.17, t = 5.59, P = 0.005; C666-1 cells: 1.37±0.12 vs. 1.06±0.06, t = 3.86, P = 0.018). The dual-luciferase reporter gene assay results indicated a targeted binding interaction between PLIN3 and ESRRA. Transmission electron microscopy observation showed that the lipid droplets in nasopharyngeal carcinoma cells increased and the binding to autophagosomes decreased after knockdown of ESRRA. The results of immunofluorescence assay demonstrated that, in contrast to the siR-NC group, there was a decrease in the co-localization of LC3 and LAMP2 and an increase in the co-localization of lipid droplets with PLIN3. Conclusions:ESRRA is highly expressed in nasopharyngeal carcinoma tissues and cells. As a transcription repressor, ESRRA may work to prevent PLIN3 from being transcribed, decrease lipid droplet stability, mediate lipophagy, and promote proliferation and migration of nasopharyngeal carcinoma cells.

Objective:To analyze the differential expression of silent information regulator transcript-1 (SIRT1) in tissues and cells of nasopharyngeal carcinoma (NPC), to explore the effects of SIRT1 on the proliferation and migration of NPC cells, as well as the effects on and mechanisms of lipid metabolism in NPC cells.Methods:Experimental subjects: In this study, tissue specimens were obtained from patients who visited the Department of Otolaryngology and performed nasopharyngeal tissue biopsy in the Affiliated Hospital of Nantong University from 2019 to 2020. Among them, 6 cases were male, 6 cases were female, age range: 27-72 years old, including 7 cases of NPC diagnosed by pathology and 5 cases of normal nasopharyngeal mucosa. Experimental methods and outcome measures: Western Blot and quantitative real time polymerase chain reaction (qRT-PCR) were used to detect the protein and mRNA levels of SIRT1. CNE2 cell line was selected for subsequent experiments. Cell viability and migratory ability were evaluated by CCK8, wound healing and Transwell assays respectively. Animal xenograft tumor model was used to explore the role of SIRT1 inhibitor Ex527 on tumor growth in nude mice. Oil red and Bodipy were used to stain intracellular lipids. For the mechanical investigation, the interactions between SIRT1 and hypoxia inducible factor-1α (HIF-1α) were analyzed by immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP). Finally, statistical analysis was performed by SPSS 26.0 software, P<0.05 was considered statistically significant. Results:The levels of SIRT1 protein (1.005±0.168) and mRNA (5.829±2.395) in NPC tissues were higher than those in normal nasopharyngeal mucosa (0.181±0.042,1.995±1.605). Differences were statistically significant ( t values were 6.438 and 2.759, both P<0.05). The mRNA and protein levels of CNE1, CNE2, 5-8F and 6-10B cell lines were also higher than those in normal nasopharynx epithelial cell line NP69. Besides, overexpression of SIRT1 correlated with the proliferation and migration of NPC cells. The tumorigenesis ability of nude mice in the Ex527 group was lower than that in the control group. The low SIRT1 expression reduced the protein level of the key enzymes of liposynthesis in NPC cells, improved the expression of lipolysis enzymes, while HIF-1α overexpression promoted lipid synthesis enzymes in NPC cells. SIRT1 inhibited HIF-1α transcription by enhancing deacetylation levels. The binding ability of HIF-1α to SIRT1 promoter regions decreased when NPC cells were hypoxic. Conclusions:SIRT1 promotes the proliferation, migration and lipid metabolism of nasopharyngeal carcinoma cells, which might be expected to provide new theoretical basis for prognosis judgment and gene therapy.

Achieving HBV DNA negative transformation and HBsAg clearance with effective antiviral therapy can reduce the incidence of HCC, but some patients are still at risk of developing HCC. Therefore, screening high-risk patients for close monitoring is essential to reduce the incidence of HCC. This paper reviews the occurrence of HCC, risk factors and risk prediction models of HBV DNA negative transformation and HBsAg clearance, and provides a basis for screening and follow-up management of high-risk group of HCC with chronic hepatitis B.

In the past 40 years,patients with primary biliary cholangitis (PBC)have benefited from the extensive use of ursodeoxycholic acid (UDCA),resulting in increase of response rate and survival rate. The prognosis of PBC patients was significantly improved. However,some patients responded poorly to UDCA and with poor long-term outcome. Therefore,accurate diagnosis,evaluation and risk stratification based on serological and pathological characteristics of the patients are very important for the treatment of PBC. This article summarized the progress in diagnosis and treatment of PBC.

Animals ; Antibodies, Monoclonal ; pharmacokinetics ; therapeutic use ; Antibodies, Viral ; therapeutic use ; Hepatitis B virus ; immunology ; Histocompatibility Antigens Class I ; metabolism ; Humans ; Macaca fascicularis ; Mice ; Protein Binding ; Protein Engineering ; Receptors, Fc ; metabolism

In recent years,ursodeoxycholic acid is commonly used for the treatment of primary biliary cholangitis (PBC);however,the growing number of PBC patients and the occurrence of suboptimal response and treatment intolerance pose a great challenge to treatment regimens.The approval of the new drug obeticholic acid brings hope to PBC patients,and a combination of fibrates also has a promising future.More studies are in progress.Although new drugs,such as monoclonal antibody,fibroblast growth factor 19,and sodium-dependent bile acid transporter inhibitor,have limited efficacy data,they provide new directions for the treatment of PBC.With the help of individualized follow-up and stratified therapy,the management of PBC patients will enter a new stage.

Humans ; Liver Diseases ; Practice Guidelines as Topic ; Prognosis

Objective:To explore therapeutic effect of esmolol hydrochloride combined amlodipine on patients with hyper-tension complicated aortic dissection (AD) and its influence on patient's blood pressure (BP) and heart rate (HR) .Meth-ods:A total of 110 patients with hypertension complicated AD were randomly and equally divided into amlodipine group and combined treatment group (received amlodipine and esmolol) .Results:Compared with before treatment , after treat-ment 0. 5 ,1. 5 and 7h ,there were significant reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both groups ,P<0.01 ,on 7h after treatment ,SBP level of combined treatment group significantly reduced than that of amlodipine group [(101.5 ± 7.8) mmHg vs .(123.4 ± 10.2) mmHg ,P<0.01];on 0.5 ,1.5 and 7h after treatment ,HR and rate pressure product (RPP) of combined treatment group significantly reduced than those of amlodipine group , P<0. 01 all. Compared with amlodipine group after treatment , there were significant rise in standard-reaching rates of BP (56.36% vs .87.27% ) ,HR (38.18% vs .92.73% ) and BP+HR (25.45% vs .81.82% ) in combined treatment group , P<0.01 all. Conclusion:Esmolol combined amlodipine can control blood pressure and heart rate rapidly ,safely and effec-tively in patients with hypertension complicated aortic dissection .

OBJECTIVE: To study the therapeutic effects of the specific immunotherapy (SIT) on allergic rhinitis and allergic rhinitis combined bronchial asthma. METHED: All patients were classified into allergic rhinitis group (AR group) with 32 patients and allergic rhinitis combined bronchial asthma group (AR+BA group) with 32 patients. Another health control group with 32 cases was designed as well. The allergens,symptom scores and therapeutic effects of the former two-group patients were analysis, and the serums of all three-group cases were extracted to evaluate the specific Immunoglobin E(sIgE), Interleukin-4 (IL-4). The SPSS13. 0 package was applied to conduct t-test and chi-square test, and the difference of P<0. 05 was regarded as statistical significance. RESULT: The main allergens of 64 patients were dermatophagoides farinae and dermatophagoides pteronyssinus. The improvement of symptom scores before and after SIT was statistical significant with P<0. 05. Although total effective rate reached 100% , AR group was superior than AR+BA group in term of the efficacy comparison, and P<0. 05 indicated the statistical significance. The serum sIgE, IL-4 values of three groups were brought into comparison, and P<0. 05 indicated the statistical significance of the difference. CONCLUSION The SIT on the AR, AR+BA is a safe and effective treatment, but different disease responds diversely. The long-term treatment course is recommended.
Allergens ; immunology ; Animals ; Asthma ; therapy ; Dermatophagoides farinae ; immunology ; Dermatophagoides pteronyssinus ; immunology ; Humans ; Immunoglobulin E ; blood ; Immunotherapy ; Interleukin-4 ; blood ; Rhinitis, Allergic ; therapy ; Treatment Outcome