MNDA expression and its value in differential diagnosis of B-cell non-Hodgkin lymphomas: a comprehensive analysis of a large series of 1293 cases.

AIMS: MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. METHODS: MNDA expression in a cohort of 1293 cases of B-NHLs and 338  cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. RESULTS: MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). CONCLUSIONS: MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

Outcomes of direct superior approach and posterolateral approach for hemiarthroplasty in the treatment of elderly patients with displaced femoral neck fractures: A comparative study.

Hemiarthroplasty is a surgical choice for super-aged patients with a high surgical risk and a sedentary lifestyle. The direct superior approach (DSA), a minimally invasive modification of the posterior approach, is rarely studied in hemiarthroplasty. The aim of the present study was to compare the clinical outcomes in elderly patients with displaced femoral neck fractures undergoing hemiarthroplasty via DSA with the conventional posterolateral approach (PLA). A total of 48 elderly patients with displaced femoral neck fractures who underwent hemiarthroplasty between February 2020 and March 2021 were retrospectively included in the study. Of them, 24 patients (mean age 84.54 ± 2.11 years) were treated with hemiarthroplasty via DSA (DSA group), while the other 24 patients (mean age 84.92 ± 2.15 years) were treated with hemiarthroplasty via PLA (PLA group). Clinical outcomes, perioperative data, and complications were recorded. There were no obvious differences in the baseline characteristics between the DSA and PLA groups, including age, gender, body mass index, Garden type, American Society of Anesthesiologists score, and hematocrit. Perioperative data showed that the length of the incision in the DSA group was smaller than that in the PLA group (p < 0.001). However, the duration of the operation and blood loss in the DSA group were longer and higher than those in the PLA group, respectively (p < 0.001). In addition, the DSA group had a shorter hospitalization time than the PLA group (p < 0.001). The visual analog scale score and Harris score 1 month postoperatively in the DSA group were better than those in the PLA group (p < 0.001). Moreover, there were no significant differences between the two groups in Harris score (for assessment dysfunction) 6 months postoperatively (p > 0.05). DSA is less invasive and has better clinical outcomes, which can allow an early return to daily living activities in elderly patients with displaced femoral neck fractures undergoing hemiarthroplasty.

Effect of Hepatocyte Growth Factor-Transfected Human Umbilical Cord Mesenchymal Stem Cells on Hepatic Stellate Cells by Regulating Transforming Growth Factor-ß1/Smads Signaling Pathway.

Studies have shown that human umbilical cord mesenchymal stem cells (hUCMSCs) could ameliorate liver fibrosis (LF) through inhibiting the activation of hepatic stellate cells (HSCs). However, the specific mechanisms have not been studied clearly. The purpose of this study was to explore the possible mechanism of hepatocyte growth factor (HGF)-transfected hUCMSCs in inhibiting the proliferation and activation of HSCs-T6. The upper and lower double-cell coculture system was established among HGF-hUCMSCs, LV5-NC-hUCMSCs, hUCMSCs, and HSCs-T6 in experimental groups; HSCs-T6 were cultured alone as control group. After coculturing for 1, 2, and 3 days, results showed that HGF-transfected hUCMSCs could decrease cell viability of HSCs-T6 and promote apoptosis; inhibit their activation and reduce the expression of Collagen I, Collagen III, TGF-ß1, Smad2 and Smad3, which may be related to inhibiting the activation of TGF-ß1/Smads signaling pathway. These findings suggested that HGF-transfected hUCMSCs may be used as an alternative and novel therapeutic approach for the treatment of LF.

Effect of Human Umbilical Cord Mesenchymal Stem Cells Transfected with HGF on TGF-ß1/Smad Signaling Pathway in Carbon Tetrachloride-Induced Liver Fibrosis Rats.

The research on human umbilical cord-derived mesenchymal stem cells (hUCMSCs) suggests promising therapeutic strategy for ameliorating liver fibrosis and it can be an effective alternative method of orthotopic liver transplantation. Hepatocyte growth factor (HGF) is the most basic cytokine involved in the inhibition of liver fibrosis and promotion of hepatocyte proliferation and regeneration. The objective of this study was to determine the possible mechanism about how the microencapsulated hUCMSCs made by alginate-poly-lysine-alginate (A-P-A) transfected with HGF could ameliorate liver fibrosis through the TGF-ß1/Smad signaling pathway. The microencapsulated cells were divided into four groups: hUCMSC (microcapsules of hUCMSCs), HGF (microcapsules of HGF+hUCMSCs), LV5-NC (microcapsules of LV5-NC, an rLV-EF1a-EGFP+Puro control lentiviral vector+hUCMSCs), and empty microcapsule (microcapsules without any hUCMSCs), and then transplanted by intraperitoneal injection into carbon tetrachloride (CCl4)-induced liver fibrosis rats, respectively. The results showed that the fibrosis in the hUCMSC, LV5-NC, and HGF groups was significantly alleviated. Moreover, the messenger RNA (mRNA) and protein levels of collagen I, collagen III, α-SMA, TGF-ß1, Smad2, and Smad3 were significantly decreased compared with the empty microcapsule group and these indices in HGF group were more decreased compared with hUCMSC and LV5-NC groups. This study indicated that microencapsulated hUCMSCs transfected with HGF could effectively improve CCl4-induced rat liver fibrosis and the possible mechanism was closely related to the inhibition of TGF-ß1/Smad signaling pathway.

Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance.

BACKGROUND: Molecular subtyping of triple-negative breast cancers (TNBCs) via gene expression profiling is essential for understanding the molecular essence of this heterogeneous disease and for guiding individualized treatment. We aim to devise a clinically practical method based on immunohistochemistry (IHC) for the molecular subtyping of TNBCs. MATERIALS AND METHODS: By analyzing the RNA sequencing data on TNBCs from Fudan University Shanghai Cancer Center (FUSCC) (n = 360) and The Cancer Genome Atlas data set (n = 158), we determined markers that can identify specific molecular subtypes. We performed immunohistochemical staining on tumor sections of 210 TNBCs from FUSCC, established an IHC-based classifier, and applied it to another two cohorts (n = 183 and 214). RESULTS: We selected androgen receptor (AR), CD8, FOXC1, and DCLK1 as immunohistochemical markers and classified TNBCs into five subtypes based on the staining results: (a) IHC-based luminal androgen receptor (IHC-LAR; AR-positive [+]), (b) IHC-based immunomodulatory (IHC-IM; AR-negative [-], CD8+), (c) IHC-based basal-like immune-suppressed (IHC-BLIS; AR-, CD8-, FOXC1+), (d) IHC-based mesenchymal (IHC-MES; AR-, CD8-, FOXC1-, DCLK1+), and (e) IHC-based unclassifiable (AR-, CD8-, FOXC1-, DCLK1-). The κ statistic indicated substantial agreement between the IHC-based classification and mRNA-based classification. Multivariate survival analysis suggested that our IHC-based classification was an independent prognostic factor for relapse-free survival. Transcriptomic data and pathological observations implied potential treatment strategies for different subtypes. The IHC-LAR subtype showed relative activation of HER2 pathway. The IHC-IM subtype tended to exhibit an immune-inflamed phenotype characterized by the infiltration of CD8+ T cells into tumor parenchyma. The IHC-BLIS subtype showed high expression of a VEGF signature. The IHC-MES subtype displayed activation of JAK/STAT3 signaling pathway. CONCLUSION: We developed an IHC-based approach to classify TNBCs into molecular subtypes. This IHC-based classification can provide additional information for prognostic evaluation. It allows for subgrouping of TNBC patients in clinical trials and evaluating the efficacy of targeted therapies within certain subtypes. IMPLICATIONS FOR PRACTICE: An immunohistochemistry (IHC)-based classification approach was developed for triple-negative breast cancer (TNBC), which exhibited substantial agreement with the mRNA expression-based classification. This IHC-based classification (a) allows for subgrouping of TNBC patients in large clinical trials and evaluating the efficacy of targeted therapies within certain subtypes, (b) will contribute to the practical application of subtype-specific treatment for patients with TNBC, and (c) can provide additional information beyond traditional prognostic factors in relapse prediction.

Somatic gene mutation signatures predict cancer type and prognosis in multiple cancers with pan-cancer 1000 gene panel.

Most cancers are caused by somatic mutations. Some common mutations in the same cancer type can form a "signature" to specifically predict the prognosis or to distinguish it from other cancers. In this study, 710 somatic cell mutations were identified in 142 cases, including digestive, lung and urogenital cancers, and the digestive cancers were further divided into liver, stomach, intestinal, esophageal and cardia cancer. The above mutations were located in 166 genes. In addition, a group of high-frequency mutation genes with specific characteristics were screened to form predictive signatures for each cancer. Verification using TCGA suggested that the signatures could predict the stages, progression-free survival, and overall survival of digestive, intestinal, and liver cancers (P < 0.05). The validation cases further confirmed the predictive role of digestive and liver cancers signatures in diagnosis and prognosis. Overall, this study established predictive signatures for different cancer systems and their subtypes. These findings enable a better understanding in cancer genome, and contribute to the personalized diagnosis and treatment.

Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis in vitro and in vivo: From biological characteristics to therapeutic mechanisms.

Liver fibrosis is a wound-healing response to chronic injuries, characterized by the excessive accumulation of extracellular matrix or scar tissue within the liver; in addition, its formation is associated with multiple cytokines as well as several cell types and a variety of signaling pathways. When liver fibrosis is not well controlled, it can progress to liver cirrhosis, but it is reversible in principle. Thus far, no efficient therapy is available for treatment of liver fibrosis. Although liver transplantation is the preferred strategy, there are many challenges remaining in this approach, such as shortage of donor organs, immunological rejection, and surgical complications. Hence, there is a great need for an alternative therapeutic strategy. Currently, mesenchymal stem cell (MSC) therapy is considered a promising therapeutic strategy for the treatment of liver fibrosis; advantageously, the characteristics of MSCs are continuous self-renewal, proliferation, multipotent differentiation, and immunomodulatory activities. The human umbilical cord-derived (hUC)-MSCs possess not only the common attributes of MSCs but also more stable biological characteristics, relatively easy accessibility, abundant source, and no ethical issues (e.g., bone marrow being the adult source), making hUC-MSCs a good choice for treatment of liver fibrosis. In this review, we summarize the biological characteristics of hUC-MSCs and their paracrine effects, exerted by secretion of various cytokines, which ultimately promote liver repair through several signaling pathways. Additionally, we discuss the capacity of hUC-MSCs to differentiate into hepatocyte-like cells for compensating the function of existing hepatocytes, which may aid in amelioration of liver fibrosis. Finally, we discuss the current status of the research field and its future prospects.

Ethogram of Yangtze finless porpoise calves (Neophocaena phocaenoides asiaeorientalis).

Underwater behavioral patterns of one Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis) calf in captivity and those performed on the water surface by two calves in semi-natural environment were focally followed and continuously recorded until one year postpartum to construct the ethogram. The results indicate that 1) the three calves could display diverse and active behavioral patterns; 2) soon after birth, patterns critical for survival appeared first; 3) playful and social patterns predominated the ethogram; 4) most of the patterns were alike across age classes; 5) most of the patterns appeared at the calves' early life stage. It is possible that the above characteristics are adaptively shaped by the aquatic and social life of this subspecies.