OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

BACKGROUND: Increasing evidence indicates that oxidative stress and interferon γ (IFNγ)-driven cellular immune responses are responsible for the pathogenesis of vitiligo. However, the connection between oxidative stress and the local production of IFNγ in early vitiligo remains unexplored. The aim of this study was to identify the mechanism underlying the production of IFNγ by mast cells and its impact on vitiligo pathogenesis. METHODS: Skin specimens from the central, marginal, and perilesional skin areas of active vitiligo lesions were collected to characterize changes of mast cells, CD8 + T cells, and IFNγ-producing cells. Cell supernatants from hydrogen peroxide (H 2 O 2 )-treated keratinocytes (KCs) were harvested to measure levels of soluble stem cell factor (sSCF) and matrix metalloproteinase (MMP)-9. A murine vitiligo model was established using Mas-related G protein-coupled receptor-B2 (MrgB2, mouse ortholog of human MrgX2) conditional knockout (MrgB2 -/- ) mice to investigate IFNγ production and inflammatory cell infiltrations in tail skin following the challenge with tyrosinase-related protein (Tyrp)-2 180 peptide. Potential interactions between the Tyrp-2 180 peptide and MrgX2 were predicted using molecular docking. The siRNAs targeting MrgX2 and the calcineurin inhibitor FK506 were also used to examine the signaling pathways involved in mast cell activation. RESULTS: IFNγ-producing mast cells were closely aligned with the recruitment of CD8 + T cells in the early phase of vitiligo skin. sSCF released by KCs through stress-enhanced MMP9-dependent proteolytic cleavage recruited mast cells into sites of inflamed skin (Perilesion vs . lesion, 13.00 ± 4.00/high-power fields [HPF] vs . 26.60 ± 5.72/HPF, P <0.05). Moreover, IFNγ-producing mast cells were also observed in mouse tail skin following challenge with Tyrp-2 180 (0 h vs . 48 h post-recall, 0/HPF vs . 3.80 ± 1.92/HPF, P <0.05). The IFNγ + mast cell and CD8 + T cell counts were lower in the skin of MrgB2 -/- mice than in those of wild-type mice (WT vs . KO 48 h post-recall, 4.20 ± 0.84/HPF vs . 0.80 ± 0.84/HPF, P <0.05). CONCLUSION Mast cells activated by MrgX2 serve as a local IFNγ producer that bridges between innate and adaptive immune responses against MCs in early vitiligo. Targeting MrgX2-mediated mast cell activation may represent a new strategy for treating vitiligo.
Vitiligo/metabolism* ; Mast Cells/immunology* ; Animals ; Interferon-gamma/metabolism* ; Mice ; Humans ; Melanocytes/metabolism* ; Receptors, G-Protein-Coupled/genetics* ; Mice, Knockout ; Mice, Inbred C57BL ; Male ; Female ; Matrix Metalloproteinase 9/metabolism* ; Stem Cell Factor/metabolism*

OBJECTIVE: To explore the clinical characteristics and prognostic factors of patients with extranasal NK/T-cell lymphoma (NKTCL). METHODS: The clinical data of 138 patients with NKTCL diagnosed in 10 medical centers of Huaihai Lymphoma Working Group from June 2015 to April 2021 were collected and analyzed retrospectively. The differences in clinicopathological characteristics of patients with different involvement and efficacy of pegaspargase regimen were compared, as well as perform survival analysis. RESULTS: A total of 138 extranasal NKTCL patients were included, with a median age of 46 years, and the ratio of males to females was approximately 2∶1. There were 39 patients with gastrointestinal involvement, 32 patients with oropharyngeal involvement, 17 patients with skin involvement, 11 patients with lymph node involvement, 11 patients with orbital involvement, and 28 patients with other parts involvement. Patients with skin involvement had a higher proportion of advanced disease and a lower proportion of CD56 positive rate compared to those with oropharyngeal involvement. Among the patients with gastrointestinal involvement, the survival rate of patients who received pegaspargase regimen was significantly higher than those who were treated without pegaspargase (P < 0.01). Multivariate analysis showed that serum creatinine was an independent prognostic factor for patients with skin involvement ( HR =1.027, 95%CI : 1.001-1.054, P =0.040), ECOG PS and EBV DNA were independent prognostic factors for patients with gastrointestinal involvement ( HR =2.635, 95%CI : 1.096-6.338, P =0.030; HR =4.772, 95% CI : 1.092-20.854, P =0.038), and ECOG PS and CA stage were independent prognostic factors for patients with oropharyngeal involvement ( HR =13.875, 95%CI : 2.517-76.496, P =0.002; HR =20.261, 95%CI : 2.466-166.470, P =0.005). CONCLUSION The clinicopathological characteristics of extranasal NKTCL patients with different sites of involvement are vary, and effective individualized treatment need to be further explored.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Asparaginase/therapeutic use* ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Prognosis ; Retrospective Studies ; Survival Rate ; Polyethylene Glycols

OBJECTIVE: To investigate the clinical features and prognostic factors of primary tonsil lymphoma (PTL). METHODS: The clinical data of 41 patients diagnosed with PTL and treated in the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2022 were collected and retrospectively analyzed. Their clinical features and prognostic factors were analyzed. RESULTS: All the 41 patients were newly diagnosed with PTL, and the median age of onset was 58(19-85) years. Among them, 19 patients started with pharyngeal pain, 12 patients presented with dysphagia, 8 patients presented with pharyngeal mass, and 2 patients presented with blurred articulation. The most common pathological type was diffuse large B-cell lymphoma (24 cases, 58.54%). All patients received chemotherapy, and 3 patients were combined with hematopoietic stem cell transplantation. Among 41 patients, 11 (26.83%) achieved complete response, 14 (34.15%) achieved partial response, and the total response rate was 60.98% (25/41). The median follow-up time was 37(6-107) months, the 5-year overall survival (OS) rate was 70.81% and 5-year progression-free survival (PFS) rate was 66.20%. Univariate analysis showed that B symptoms, Ki-67, β₂-MG and IPI score had significant effects on PFS and OS of patients (all P < 0.05). Multivariate analysis showed that IPI score was an independent risk factor for PFS and OS of patients (P < 0.05). CONCLUSION The clinical manifestations of PTL lack specificity, and the prognosis is relatively good. Most patients can achieve long-term survival after treatment. IPI score is related to the prognosis.
Tonsillar Neoplasms/pathology* ; Lymphoma/pathology* ; Humans ; Prognosis ; Retrospective Studies ; Drug Therapy ; Progression-Free Survival ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Lymphoma, B-Cell/pathology* ; Survival Rate

The autonomic nervous system imbalance caused by the overactivation of the sympathetic nerve and the weakened activity of the parasympathetic nerve is closely related to the occurrence and development of myocardial infarction.Autonomic nerve regulation is a new therapeutic approach aiming at inhibiting sympathetic activity and increasing parasympathetic activity.It encompasses magnetic nerve stimulation,optogenetic neuromodulation,and microinjection of botulinum toxin,which could promote the rebalance of the autonomic nervous system,thereby curbing the deterioration of the cardiac function and reducing the occurrence of ventricular arrhythmias after myocardial infarction.This paper reviews the anatomical basis,mechanisms of action,and research advances in intervention strategies of the autonomic nervous system in myocardial infarction.
Humans ; Myocardial Infarction/physiopathology* ; Autonomic Nervous System/physiopathology* ; Autonomic Pathways

To promote the standardization and normalization of perioperative care for follicular unit extraction(FUE) hair transplantation, ensure treatment efficacy, and align with advancements in the specialty, the Nursing Branch of the Chinese Association of Plastic and Aesthetics organized a panel of domestic experts. By integrating evidence-based medicine with clinical practice experience, and following thorough discussions, these experts developed the Clinical Practice Expert Consensus on Perioperative Nursing Care for Follicular Unit Extraction (2025). This consensus provides a comprehensive overview of hair transplantation, covering preoperative preparation, surgical procedures, intraoperative coordination, postoperative management, and complication prevention and treatment. It serves as a key reference and guide for implementing standardized perioperative nursing care in FUE hair transplantation.

Early start denver model(ESDM)is a comprehensive early intervention approach for the children with autism spectrum disorder(ASD)between 12-month-old-36-month-old.The model is built upon the theoretical foundations of applied behavior analysis,denver model(DM),and pivotal response treatment,and it is one of the naturalistic developmental behavioral interventions.Compared with the other early intervention methods,ESDM is not limited by the environment of intervention;it encompasses all the areas of development during teaching practice and has been widely adopted for the early intervention of the children with ASD,and achieves the satisfactory therapeutic effect.The ESDM typically uses an intensive one-on-one intervention approach,but variabilities have emerged in its practical application,such as group ESDM(G-ESDM),parent-implemented ESDM(P-ESDM),and peer-mediated ESDM.In particular,G-ESDM and P-ESDM have provided the learning opportunities for more families,showing a broad application prospect.This study reviews the theoretical foundations,teaching models,and the effects of various intervention modalities of the ESDM in the treatment of ASD;combined with the domestic and international research findings,this study offers a reference for further studies on the mechanism of ESDM intervention for ASD.

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

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.