BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Objectives:To investigate the relationship between paraspinal muscle degeneration and isthmic spondylolisthesis in L5/S1.Methods:The clinical data of 108 patients with L5/S1 bilateral isthmic spondylolysis admitted and treated at the Department of Orthopedics,the First Affiliated Hospital of Zhengzhou University from January 1,2020 to December 31,2023 were retrospectively analyzed.There were 62 females and 46 males,aged 26-86(52.8±10.4)years.All the patients had complete imaging data,including lateral and dynamic lumbar X-ray,lumbar CT and lumbar MRI.According to the presence or absence of spondylolisthesis and Meyerding grading,the patients were divided into non-spondylolisthesis group(28 cases),grade Ⅰ spondylolisthesis group(46 cases)and grade n spondylolisthesis group(34 cases).Venebral body cross-sectional area(V CSA),erector spinae muscle cross-sectional area(ES CSA),multifidus muscle cross-sectional area(MF CSA),and facet joint angle(FJA)were measured at the inferior vertebral endplate of L5 vertebral body on the axial view of lumbar spine MRI.And the mean FJA(mFJA),relative MF CSA(MF rCSA),relative ES CSA(ES rCSA),fat infiltration rate of multifidus muscle(MF FIR)and fat infiltration rate of erector spinae muscle(ES FIR)were calculated.The differences in age,gender,body mass index(BMI),disease duration,V CSA,mFJA,MF CSA,ES CSA,MF rCSA,ES rCSA,MF FIR and ES FIR between the three groups were compared.Ordinal logistics regression was used to analyze the relationship between age,gender,disease duration,BMI,mFJA,MF rCSA,ES rCSA,MF FIR,ES FIR and the isthmic spondylolisthesis.Results:There were no statistical differences in age,body weight,BMI,V CSA,and mFJA between the three groups(P＞0.05).The proportion of female patients in the non-spondylolisthesis group(29％)was significantly lower than that in grade Ⅰ spondylolisthesis group(61％)and grade Ⅱ spondylolisthesis group(76％)(P＜0.05).The height of non-spondylolisthesis group(1.68±0.06m)was higher than that of grade Ⅰ spondylolisthesis group(1.64±0.75m)and grade Ⅱ spondylolisthesis group(1.63±0.54m)(P＜0.05),and the disease duration in the non-spondylolisthesis group was shorter than that of grade Ⅰ spondylolisthesis group and grade Ⅱspondylolisthesis group(P＜0.05).There was no significant difference in MF CSA,MF rCSA and ES FIR between the three groups(P＞0.05).ES CSA and ES rCSA in grade Ⅱ spondylolisthesis group(3183.2±1196.38mm2 and 2.14±1.11)were significantly greater than that in grade Ⅰ spondylolisthesis group(2579.28±896.56mm2 and 1.65±0.65)and non-spondylolisthesis group(2401.40±742.98mm2 and 1.56±0.58)(P＜0.05).The MF FIR of grade Ⅱ spondylolisthesis group(40.70±14.05)％was significantly higher than that of grade Ⅰspondylolisthesis group(30.39±12.98)％and non-spondylolisthesis group(26.69±9.96)％(P＜0.05).There were no significant differences in ES CSA,ES rCSA and MF FIR between grade Ⅰ spondylolisthesis group and non-spondylolisthesis group(P＞0.05).Ordinal logistics regression analysis showed that female(OR=2.81;95％CI:1.120-7.062;P=0.028)and increased MF FIR(OR=1.044;95％CI:1.003-1.088;P=0.034)were the independent risk factors for the progression of isthmic spondylolisthesis(P＜0.05).Conclusions:Patients with a higher degree of isthmic spondylolisthesis have more severe fat infiltration of multifidus muscle and hypertrophy of erector spinae muscle.Female and increased MF FIR are independent risk factors for the progression of isthmic spondylolisthesis.

[Objective] To explore the activity aberration of primary insomnia (PI) patients with resting-state fMRI.[Methods]Resting-state fMRI datasets of 60 PI and 60 healthy controls were acquired.We investigated the cortical connectivity patterns of the insula in PI and independent-sample t-test were used to compare the brain activity abnormalities between two groups.[Results] In PI,we found enhanced connectivity between left insular with the left middle cingulate cortex,the Frontal_Sup_Media and right Parietal_Inf,as well as decreased connectivity with the left precentral gyrusand the right fusiformgyrus (P ＜ 0.05).The right insular show increased FC with the right middle cingulate cortex,the right fusiform gyrus and the right middle frontal gyrus,as well as decreased FC with the right precentral gyrus and the right middle temporal gyrus (P ＜ 0.05).[Conclusion] This study provides additional evidence of brain functional integration alterations in PI.Those may help us understand the possible neural mechanisms of PI.