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*

At present,breast cancer is still the first place in the global incidence and mortality of female cancer.Searching for reliable biological markers plays an extremely important role in clarifying the early diagnosis of breast cancer and improving the long-term survival rate and prognosis of breast cancer patients.In recent years,long non-coding RNA HOTAIR(LncRNA HOTAIR)is still the focus of research by many scholars,and HOTAIR is closely related to the occurrence and development of a variety of malignant tumors.The expression of HOTAIR is particularly obvious in breast cancer patients.More and more studies have shown that HOTAIR is highly expressed in both peripheral blood and breast cancer tissues of breast cancer patients,and is closely related to the proliferation,metastasis and drug resistance of breast cancer.HOTAIR may become an important biomarker for the early diagnosis of breast cancer and a target for breast cancer treatment.

At present,breast cancer is still the first place in the global incidence and mortality of female cancer.Searching for reliable biological markers plays an extremely important role in clarifying the early diagnosis of breast cancer and improving the long-term survival rate and prognosis of breast cancer patients.In recent years,long non-coding RNA HOTAIR(LncRNA HOTAIR)is still the focus of research by many scholars,and HOTAIR is closely related to the occurrence and development of a variety of malignant tumors.The expression of HOTAIR is particularly obvious in breast cancer patients.More and more studies have shown that HOTAIR is highly expressed in both peripheral blood and breast cancer tissues of breast cancer patients,and is closely related to the proliferation,metastasis and drug resistance of breast cancer.HOTAIR may become an important biomarker for the early diagnosis of breast cancer and a target for breast cancer treatment.

Objective To analyze the factors influencing axillary lymph-node metastasis(ALNM)in microinvasive breast cancer(MIBC)patients,as well as to establish the risk-prediction model of ipsilateral ALNM in MIBC patients.Methods A total of 4475 primary female MIBC diagnosed by pathology from 2010 to 2015 were searched and screened from the SEER database.The obtained data were used to establish a prediction model for ALNM of MIBC.A total of 2266 primary female MIBC patients diagnosed by pathology from 2018 to 2020 in the SEER database were screened as the external validation cohort.The clinicopathological data of the enrolled MIBC patients were collected.Univariate analysis was used to screen out the factors affecting ALNM in MIBC patients.Statistically significant variables in univariate analysis were included in multivariate logistic regression analysis.The independent factors influencing ALNM in MIBC patients were screened out,and a nomogram was established.The area under the curve(AUC)was calculated by plotting the ROC curve.After plotting the calibration curve,the model was evaluated by Hosmer-Lemeshow goodness-of-fit test.Results A total of 309 patients were diagnosed with ipsilateral ALNM among the 6741 MIBC patients,accounting for about 4.58%.Univariate analysis of the modeling group showed that age,ethnicity,histological grade,pathological type,molecular subtype,and lateral side were associated with ALNM in MIBC patients(P<0.05).Results of multivariate analysis showed that the risk of ALNM was higher in MIBC patients≤40 years old,black people,histological grade Ⅱand Ⅲ,and primary right side(P<0.05).Subtype is an independent factor influencing ALNM in MIBC patients.However,the difference in ALNM risk was not statistically significant between the subtype of HR+HER2+,HR-HER2+,HR-HER2-and HR+HER2-subtypes.The AUC of the modeling group was 0.716(95%CI:0.682-0.750),the best cut-off value was 0.045,the sensitivity was 0.733,and the specificity was 0.608.The newly established nomogram model was used for the validation cohort,and its AUC was 0.722(95%CI:0.667-0.777).The P values of the Hosmer-Lemeshow goodness-of-fit test of the calibration curves in the modeling and validation groups exceeded 0.05.Conclusion The risk-prediction model of ALNM in MIBC patients established by the SEER database has good predictive ability and can thus be expected to serve as a reference for clinical practice.

Interleukin-34(IL-34)is a member of the interleukin family and functions primarily as a macrophage growth factor.It plays a role in a variety of inflammatory and immune diseases by binding to specific receptors to activate multiple signaling pathways,thereby regulating target immune cell activity.Studies have shown the involvement of IL-34 in cutaneous immunoregulation,particularly in the pathogenesis of atopic dermatitis(AD).The expression level of IL-34 is significantly reduced in the lesional skin of AD patients,and its role as a potential negative regulator may function by modulating the levels of inflammatory factors and skin barrier components.Increasing local IL-34 levels in the skin may help to limit the progression of the inflammatory response.Therefore,in order to better understand the role of IL-34 in the pathogenesis of AD and to explore its potential as a therapeutic target,this article reviews the signal transduction mechanism,biological characteristics and the role of IL-34 in AD.

Objective To explore the impact of clinical treatment decisions on the long-term survival of different molecular subtypes of locally advanced breast cancer(LABC),and to promote the development of more effective and individualized treatment regimens for LABC.Methods The cases of LABC diagnosed by pathology from 2010 to 2015 were searched in the database.Breast cancer-specific survival(BCSS)and overall survival(OS)were estimated by plotting Kaplan-Meier curves.The log rank test(Mantel-Cox)was used to analyze the difference between the groups,and the benefit population of LABC was determined after for age,TNM stage,grade,treatment methods.Results The 5-year OS and BCSS were 77.43％and 84.34％in breast-conserving,and 68.03％and 76.90％in mastectomy,respectively.The 5-year OS and BCSS of Luminal A LABC were 79.91％and 87.23％in breast-conserving,and 71.78％and 81.16％in mastectomy,respectively.The 5-year OS and BCSS of Luminal B LABC were 79.30％and 83.14％in breast-conserving,and were 70.37％and 76.92％in mastectomy,respectively.The 5-year OS and BCSS of triple-negative LABC were 60.77％and 68.13％in breast-conserving,and those of mastectomy were 47.13％and 55.94％,respectively.The 5-year OS and BCSS of HER2 positive were 75.42％,82.05％in breast-conserving,and were 67.05％and 75.01％in mastectomy,respectively;The 5-year OS and BCSS of triple-positive LABC were 86.12％and 91.63％in breast-conserving,and 74.54％and 82.56％in mastectomy,respectively.The 5-year OS and BCSS of well differentiated and N0 triple-positive LABC patients with chemotherapy were 88.24％and 76.91％,and those of patients without chmotherapy were 88.24％and 90.91％,respectively(BCSS:P=0.812;OS:P=0.311).Conclusion In the selective population,OS and BCSS of patients with LABC undergoing breast conserving surgery were significantly better than those of mastectomy.When OS and BCSS were compared for different molecular types and stages of LABC,breast-conserving surgery was still superior to total mastectomy.LABC could be considered for highly differentiated,N0 stage Triple positive without chemotherapy.

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Background: Feline panleukopenia virus (FPV) is a widespread and highly infectious pathogen in cats with a high mortality rate. Although Yanji has a developed cat breeding industry, the variation of FPV locally is still unclear. Objectives: This study aimed to isolate and investigate the epidemiology of FPV in Yanji between 2021 and 2022. Methods: A strain of FPV was isolated from F81 cells. Cats suspected of FPV infection (n = 80) between 2021 and 2022 from Yanji were enrolled in this study. The capsid protein 2 (VP2) of FPV was amplified. It was cloned into the pMD-19T vector and transformed into a competent Escherichia coli strain. The positive colonies were analyzed via VP2 Sanger sequencing. A phylogenetic analysis based on a VP2 coding sequence was performed to identify the genetic relationships between the strains. Results: An FPV strain named YBYJ-1 was successfully isolated. The virus diameter was approximately 20–24 nm, 50% tissue culture infectious dose = 1 × 10 −4.94 /mL, which caused cytopathic effect in F81 cells. The epidemiological survey from 2021 to 2022 showed that 27 of the 80 samples were FPV-positive. Additionally, three strains positive for CPV-2c were unexpectedly found. Phylogenetic analysis showed that most of the 27 FPV strains belonged to the same group, and no mutations were found in the critical amino acids. Conclusions A local FPV strain named YBYJ-1 was successfully isolated. There was no critical mutation in FPV in Yanji, but some cases with CPV-2c infected cats were identified.

Objective: To evaluate 3D imaging technology in the preoperative evaluation of breast conserving surgery. Methods: A ret-rospective analysis was conducted using clinical data from 38 patients who underwent breast conserving surgery that was assisted by 3D imaging technology in Xiaogan Hospital Affiliated to Wuhan University of Science and Technology from April 2017 to January 2019. All 38 patients underwent 3.0-T breast magnetic resonance imaging (MRI) examination before surgery, and 3D reconstruction of virtu-al images was constructed through 3D modeling of medical digital imaging and communication (DICOM) data. The predicted resected tissue volume was compared with the volume of the actual resected specimen, and the surgical margin and postoperative aesthetics of the breast conserving surgery were evaluated. Results: The reconstructed 3D model clearly displayed the anatomical structures of the breast, tumor, gland, and blood vessels, and their relationship in 3D spaces. The goodness of fit of the 3D model to the practical sit-uation was 97.4% (37/38). In terms of the resection tissue volume, there was no significant difference between the predicted results (PRTV) and actual results (ARTV) [(61.7 ± 20.1) mL vs. (65.1 ± 20.7) mL, P>0.05]. There was a strong positive correlation between ARTV and PRTV (P<0.01). One patient underwent supplementary secondary surgery, resulting in an incidence of 2.6% (1/38). The postopera-tive satisfaction for breast conserving surgery was 100% (38/38). Conclusions: 3D imaging technology clearly displays the anatomical relationship between breast tumor and surrounding tissues, and correctly assesses breast volume, guiding surgical resection.

OBJECTIVE: To compare the long-term survival outcomes of Siewert II adenocarcinoma of esophagogastric junction (AEG) between transthoracic (TT) approach and transabdominal (TA) approach. METHODS: The databases of Gastrointestinal Surgery Department and Thoracic Surgery Department in West China Hospital of Sichuan University from 2006 to 2014 were integrated. Patients of Siewert II AEG who underwent resection were retrospectively collected. INCLUSION CRITERIA: (1) adenocarcinoma confirmed by gastroscopy and biopsy; (2) tumor involvement in the esophagogastric junction line; (3) tumor locating from lower 5 cm to upper 5 cm of the esophagogastric junction line, and tumor center locating from upper 1 cm to lower 2 cm of esophagogastric junction line; (4)resection performed at thoracic surgery department or gastrointestinal surgery department; (5) complete follow-up data. Patients at thoracic surgery department received trans-left thoracic, trans-right thoracic, or transabdominothoracic approach; underwent lower esophagus resection plus proximal subtotal gastrectomy; selected two-field or three-field lymph node dissection; underwent digestive tract reconstruction with esophagus-remnant stomach or esophagus-tubular remnant stomach anastomosis above or below aortic arch using hand-sewn or stapler instrument to perform anastomosis. Patients at gastrointestinal surgery department received transabdominal(transhiatal approach), or transabdominothoracic approach; underwent total gastrectomy or proximal subtotal gastrectomy; selected D1, D2 or D2 lymph node dissection; underwent digestive tract reconstruction with esophagus-single tube jejunum or esophagus-jejunal pouch Roux-en-Y anastomosis, or esophagus-remnant stomach or esophagus-tubular remnant stomach anastomosis; completed all the anastomoses with stapler instruments. The follow-up ended in January 2018. The TNM stage system of the 8th edition UICC was used for esophageal cancer staging; survival table method was applied to calculate 3-year overall survival rate and 95% cofidence interval(CI); log-rank test was used to perform survival analysis; Cox regression was applied to analyze risk factors and calculate hazard ratio (HR) and 95%CI. RESULTS: A total of 443 cases of Siewert II AEG were enrolled, including 89 cases in TT group (with 3 cases of transabdominothoracic approach) and 354 cases in TA group. Median follow-up time was 50.0 months (quartiles:26.4-70.2). The baseline data in TT and TA groups were comparable, except the length of esophageal invasion [for length <3 cm, TA group had 354 cases(100%), TT group had 44 cases (49.4%), χ²=199.23,P<0.001]. The number of harvested lymph node in thoracic surgery department and gastrointestinal surgery department were 12.0(quartiles:9.0-17.0) and 24.0(quartiles:18.0-32.5) respectively with significant difference (Z=11.29,P<0.001). The 3-year overall survival rate of TA and TT groups was 69.2%(95%CI:64.1%-73.7%) and 55.8% (95%CI:44.8%-65.4%) respectively, which was not significantly different by log-rank test (P=0.059). However, the stage III subgroup analysis showed that the survival of TA group was better [the 3-year overall survival in TA group and TT group was 78.1%(95%CI:70.5-84.0) and 46.3%(95%CI:31.0-60.3) resepectively(P=0.001)]. Multivariate Cox regression analysis revealed that the TT group had poor survival outcome (HR=2.45,95%CI:1.30-4.64, P=0.006). CONCLUSION The overall survival outcomes in the TA group are better, especially in stage III patients, which may be associated with the higher metastatic rate of abdominal lymph node and the more complete lymphadenectomy via TA approach.
Adenocarcinoma ; classification ; mortality ; pathology ; surgery ; China ; Databases, Factual ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagectomy ; methods ; Esophagogastric Junction ; pathology ; surgery ; Gastrectomy ; methods ; Humans ; Laparotomy ; Lymph Node Excision ; methods ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms ; classification ; mortality ; pathology ; surgery ; Survival Analysis ; Thoracic Surgical Procedures