Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma.

Multiple myeloma (MM) remains incurable due to drug resistance. Ribosomal protein S3 (RPS3) has been identified as a non-Rel subunit of NF-κB. However, the detailed biological roles of RPS3 remain unclear. Here, we report for the first time that RPS3 is necessary for MM survival and drug resistance. RPS3 was highly expressed in MM, and knockout of RPS3 in MM inhibited cell growth and induced cell apoptosis both in vitro and in vivo. Overexpression of RPS3 mediated the proteasome inhibitor resistance of MM and shortened the survival of MM tumor-bearing animals. Moreover, our present study found an interaction between RPS3 and the thyroid hormone receptor interactor 13 (TRIP13), an oncogene related to MM tumorigenesis and drug resistance. We demonstrated that the phosphorylation of RPS3 was mediated by TRIP13 via PKCδ, which played an important role in activating the canonical NF-κB signaling and inducing cell survival and drug resistance in MM. Notably, the inhibition of NF-κB signaling by the small-molecule inhibitor targeting TRIP13, DCZ0415, was capable of triggering synergistic cytotoxicity when combined with bortezomib in drug-resistant MM. This study identifies RPS3 as a novel biomarker and therapeutic target in MM.

The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13-MAPK-YWHAE signaling pathway.

BACKGROUND: Multiple myeloma (MM), an incurable disease owing to drug resistance, requires safe and effective therapies. Norcantharidin (NCTD), an active ingredient in traditional Chinese medicines, possesses activity against different cancers. However, its toxicity and narrow treatment window limit its clinical application. In this study, we synthesized a series of derivatives of NCTD to address this. Among these compounds, DCZ5417 demonstrated the greatest anti-MM effect and fewest side effects. Its anti-myeloma effects and  the mechanism were further tested. METHODS: Molecular docking, pull-down, surface plasmon resonance-binding, cellular thermal shift, and ATPase assays were used to study the targets of DCZ5417. Bioinformatic, genetic, and pharmacological approaches were used to elucidate the mechanisms associated with DCZ5417 activity. RESULTS: We confirmed a highly potent interaction between DCZ5417 and TRIP13. DCZ5417 inhibited the ATPase activity of TRIP13, and its anti-MM activity was found to depend on TRIP13. A mechanistic study verified that DCZ5417 suppressed cell proliferation by targeting TRIP13, disturbing the TRIP13/YWHAE complex and inhibiting the ERK/MAPK signaling axis. DCZ5417 also showed a combined lethal effect with traditional anti-MM drugs. Furthermore, the tumor growth-inhibitory effect of DCZ5417 was demonstrated using in vivo tumor xenograft models. CONCLUSIONS: DCZ5417 suppresses MM progression in vitro, in vivo, and in primary cells from drug-resistant patients, affecting cell proliferation by targeting TRIP13, destroying the TRIP13/YWHAE complex, and inhibiting ERK/MAPK signaling. These results imply a new and effective therapeutic strategy for MM treatment.

A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway.

Multiple myeloma (MM), the second most common haematological malignancy, is currently incurable because patients often develop multiple drug resistance and experience subsequent relapse of the disease. This study aims to identify a potential therapeutic agent that can counter bortezomib (BTZ) resistance in MM. DCZ0358, a novel alkaloid compound, is found to exert potent cytotoxic effects against BTZ-resistant MM cells in vivo and in vitro. The anti-myeloma activity of DCZ0358 is associated with inhibition of cell proliferation, promotion of cell apoptosis via caspase-mediated apoptotic pathways, and induction of G0/G1 phase arrest via downregulation of cyclin D1, CDK4, and CDK6. Further investigation of the molecular mechanism shows that DCZ0358 suppresses the JAK2/STAT3 signaling pathway. In conclusion, DCZ0358 can successfully counter BTZ resistance in MM cells. This study provides evidence that warrants future preclinical assessments of DCZ0358 as a therapeutic agent against BTZ resistance in MM.

Dihydrocelastrol induces antitumor activity and enhances the sensitivity of bortezomib in resistant multiple myeloma by inhibiting STAT3-dependent PSMB5 regulation.

Multiple myeloma (MM) is characterized by excessive aggregation of B-cell-derived malignant plasma cells in the hematopoietic system of bone marrow. Previously, we synthesized an innovative molecule named dihydrocelastrol (DHCE) from celastrol, a triterpene purified from medicinal plant Tripterygium wilfordii. Herein, we explore the therapeutic properties and latent signal transduction mechanism of DHCE action in bortezomib (BTZ)-resistant (BTZ-R) MM cells. In this study, we first report that DHCE shows antitumor activities in vitro and in vivo and exerts stronger inhibitory effects than celastrol on BTZ-R cells. We find that DHCE inhibits BTZ-R cell viability by promoting apoptosis via extrinsic and intrinsic pathways and suppresses BTZ-R MM cell proliferation by inducing G0/G1 phase cell cycle arrest. In addition, inactivation of JAK2/STAT3 and PI3K/Akt pathways are involved in the DHCE-mediated antitumor effect. Simultaneously, DHCE acts synergistically with BTZ on BTZ-R cells. PSMB5, a molecular target of BTZ, is overexpressed in BTZ-R MM cells compared with BTZ-S MM cells and is demonstrated to be a target of STAT3. Moreover, DHCE downregulates PSMB5 overexpression in BTZ-R MM cells, which illustrates that DHCE overcomes BTZ resistance through increasing the sensitivity of BTZ in resistant MM via inhibiting STAT3-dependent PSMB5 regulation. Overall, our findings imply that DHCE may become a potential therapeutic option that warrants clinical evaluation for BTZ-R MM.

Temporal characterization of electron dynamics in attosecond XUV and infrared laser fields.

We use a Wigner distribution-like function based on the strong field approximation theory to obtain the time-energy distributions and the ionization time distributions of electrons ionized by an XUV pulse alone and in the presence of an infrared (IR) pulse. In the case of a single XUV pulse, although the overall shape of the ionization time distribution resembles the XUV-envelope, its detail shows dependence on the emission direction of the electron and the carrier-envelope phase of the pulse, which mainly results from the low-energy interference structure. It is further found that the electron from the counter-rotating term plays an important role in the interference. In the case of the two-color pulse, both the time-energy distributions and the ionization time distributions change with varying IR field. Our analysis demonstrates that the IR field not only modifies the final electron kinetic energy but also changes the electron's emission time, which is attributed to the change of the electric field induced by the IR pulse. Moreover, the ionization time distributions of the photoelectrons emitted from atoms with higher ionization energy are also given, which show less impact of the IR field on the electron dynamics.

Young children selectively ignore quality to promote self-interest.

Although there has been extensive research on how children distribute resources with respect to quantity, little is known about how these decisions are affected by resource quality. The current research addressed this question by conducting two preregistered studies in which 3-, 5-, and 7-year-old children (total N = 360) made anonymous distributions of high-quality and low-quality items. Quantitative fairness entailed distributing an equal number of items irrespective of quality, and qualitative fairness entailed distributing equal numbers of high-quality and low-quality items. In Study 1, a majority of 7-year-olds distributed resources equally between themselves and another child in terms of both quality and quantity, whereas a majority of 3- and 5-year-olds did so only in terms of quantity while giving themselves a qualitative advantage. In Study 2, a majority of children in all three age groups distributed resources equally between two other children in terms of both quality and quantity. Together with prior findings, these results suggest that children selectively ignore the dimension of quality when it serves their own interests. The results also show, for the first time, that by 7 years of age children consider quality even at the expense of their own interests and that children as young as 3 years have the capacity to take into account resource quality when making distributions.

Comparison Study of Strong-Field Ionization of Molecules and Atoms by Bicircular Two-Color Femtosecond Laser Pulses.

We experimentally investigate the single and double ionization of N_{2} and O_{2} molecules in bicircular two-color femtosecond laser pulses, and compare with their companion atoms of Ar and Xe with comparable ionization thresholds. Electron recollision assisted enhanced ionization is observed in N_{2} and Ar by controlling the helicity and field ratio between the two colors, whereas the enhanced ionization via the recollision is almost absent in O_{2} and Xe. Our S-matrix simulations clearly reveal the crucial role of the detailed electronic structures of N_{2} and O_{2} on the two-dimensional recollision of the electrons driven by the bicircular two-color laser fields. As compared to Ar, the resonant multiphoton excitation dominates the double ionization of Xe.

A bioinformatic analysis found low expression and clinical significance of ATF4 in breast cancer.

Background: Activating Transcription Factor 4 (ATF4) expression exhibits differential patterns across different types of tumors. Besides, the pathogenesis of breast cancer is complex, and the exact relationship between ATF4 and ATF4 remains uncertain. Methods: The analysis of ATF4 expression was conducted by utilizing The Cancer Genome Atlas (TCGA) pan-cancer data, while the gene expression profile of breast cancer was checked by the comprehensive database-Gene Expression Omnibus database. In order to gain a more comprehensive understanding of the specific cell types that exhibit ATF4 expression within the microenvironment of breast cancer, we conducted a single-cell analysis of ATF4 using two distinct datasets of human breast cancer (GSE114717 and GSE11088, respectively). The spatial distribution of ATF4 within a tissue was demonstrated based on datasets obtained from the Human Protein Atlas (HPA) and SpatialDB. The clinical prognostic significance of ATF4 was assessed by analyzing clinical survival data obtained from TCGA, GSE4830, and GSE25055 datasets. We used the R package clusterProfiler to carry out an enrichment analysis of ATF4. We assessed how ATF4 impacts the growth and movement of breast cancer cell lines. We manipulated ATF4 levels using plasmid transfection techniques. Results: The expression of ATF4 was found to be suboptimal and demonstrated a significant correlation with enhanced disease-specific survival (p = 0.012) and overall survival (p = 0.032) in breast cancer as well as other malignancies. We conducted an analysis to investigate the interaction between the infiltration level of immune cells and the expression of ATF4, using samples obtained from TCGA with known immune cell infiltration scores. Furthermore, a notable positive correlation exists between the elevated expression of ATF4 and immune-related genomes, specifically those associated with chemokine as well as immunity. Subsequent examination revealed a notable augmentation in the cytodifferentiation of T cells into regulatory T (Treg) cells within tissues exhibiting elevated levels of ATF4 expression. ATF4 exhibits notable upregulation in the MDA-MB-231 cell, thereby exerting a substantial impact on cell proliferation and migration upon its knockdown. Conversely, the overexpression of ATF4 in the MCF7 Luminal A breast cancer cell line can also modulate cellular function. Conclusions: Our study suggests that ATF4 helps T cells differentiate into Treg cells in breast cancer. ATF4 can represent a clinically useful biomarker to predict the overall survival rate, especially in patients with different subtypes of breast cancer. Provide certain guidance value for the development of targeted drugs or inhibitors targeting ATF4.

A novel pterostilbene compound DCZ0825 induces macrophage M1 differentiation and Th1 polarization to exert anti-myeloma and immunomodulatory.

Multiple myeloma (MM) is an incurable and recurrent malignancy characterized by abnormal plasma cell proliferation. There is an urgent need to develop effective drugs in MM. DCZ0825 is a small molecule compound derived from pterostilbene with direct anti-myeloma activity and indirect immune-killing effects though reversal of the immunosuppression. DCZ0825 inhibits the activity and proliferation of MM cells causing no significant toxicity to normal cells. Using flow cytometry, this study found that DCZ0825 induced caspase-dependent apoptosis in MM cells and arrested the cell cycle in the G2/M phase by down-regulating CyclinB1, CDK1 and CDC25. Moreover, DCZ0825 up-regulated IRF3 and IRF7 to increase IFN-γ, promoting M2 macrophages to transform into M1 macrophages, releasing the immunosuppression of CD4T cells and stimulated M1 macrophages and Th1 cells to secrete more INF-γ to form immune killing effect on MM cells. Treatment with DCZ0825 resulted in an increased proportion of positive regulatory cells such as CD4T, memory T cells, CD8T, and NK cells, with downregulation of the proportion of negative regulatory cells such as Treg cells and MDSCs. In conclusion, DCZ0825 is a novel compound with both antitumor and immunomodulatory activity.

Alignment-dependent fluorescence emission induced by tunnel ionization of carbon dioxide from lower-lying orbitals.

The study of the ionization process of molecules in an intense infrared laser field is of paramount interest in strong-field physics and constitutes the foundation of imaging of molecular valence orbitals and attosecond science. We show measurement of alignment-dependent ionization probabilities of the lower-lying orbitals of the molecules by experimentally detecting the alignment dependence of fluorescence emission from tunnel ionized carbon dioxide molecules. The experimental measurements are compared with the theoretical calculations of the strong field approximation and molecular Ammosov-Delone-Krainov models. Our results demonstrate the feasibility of an all-optical approach for probing the ionization dynamics of lower-lying orbitals of molecules, which is until now still difficult to achieve by other techniques. Moreover, the deviation between the experimental and theoretical results indicates the incompleteness of current theoretical models for describing strong field ionization of molecules.

Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells.

The most common neoplasm among adult lymphomas is diffuse large B-cell lymphoma (DLBCL), typically characterized by pain-free and progressive lymph node enlargement. Due to high heterogeneity of DLBCL, 30-40 % of patients are resistant to R-CHOP standard chemoimmunotherapy. DCZ0358 is a new compound designed and synthesized from berberine by our group and the molecular mechanism by which it inhibited DLBCL growth has attracted our widespread attention. In this study, we employed the CCK8 assay to reveal that DCZ0358 inhibited proliferation in a dependent manner of time and dosage of DLBCL cells. Moreover, flowcytometry and western blot results showed that DCZ0358 downregulated the expression of CDK4, CDK6 and CyclinD1 to block cell cycle progression in G0/G1 phase. Furthermore, DCZ0358 enhanced mitochondrial membrane potential depolarization, promoted mitochondrial permeability transport pore openness, increased cytoplastic Ca2+ levels and decreased intracellular adenosine triphosphate production, which led to mitochondrial dysfunction. In particular, DCZ0358 treatment triggered cell apoptosis and elevated intracellular reactive oxygen species (ROS) levels, which subsequently mediated JNK pathway activation. Further research indicated the pre-treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358. Most importantly, DCZ0358 exhibited synergistic anti-tumor effects when combined with etoposide, a common clinical anti-DLBCL drug, both in vitro and certainly in vivo. Above results demonstrated anti-tumor molecular mechanism of DCZ0358 in DLBCL cells and highlighted the ROS/JNK/DNA damage pathway as a potential target in therapies, which have implications for the development of more effective clinical treatments for DLBCL.

Ionization suppression of diatomic molecules in an intense midinfrared laser field.

Diatomic molecules (e.g., O(2)) in an intense laser field exhibit a peculiar suppressed ionization behavior compared to their companion atoms. Several physical models have been proposed to account for this suppression, while no consensus has been achieved. In this Letter, we aim to clarify the underlying mechanisms behind this molecular ionization suppression. Experimental data recorded at midinfrared laser wavelength and its comparison with that at near-infrared wavelength revealed a peculiar wavelength and intensity dependence of the suppressed ionization of O(2) with respect to its companion atom of Xe, while N(2) behaves like a structureless atom. It is found that the S-matrix theory calculation can reproduce well the experimental observations and unambiguously identifies the significant role of two-center interference effect in the ionization suppression of O(2).

Predictive Value Analysis of Serum Ig A, Ig G, and TNF-α in Recurrence of Multiple Myeloma.

Objective: The study is aimed at analyzing the predictive value of serum Ig A, Ig G, and TNF-α in the recurrence of multiple myeloma (MM). Methods: 136 patients with MM treated in our hospital from January 2010 to January 2017 were followed up for 5 years. Finally, 100 patients who met the inclusion and exclusion criteria and had the complete follow-up visit were selected as the study subjects, with the recurrence of MM as endpoint event, and the observation was taken until the occurrence of endpoint event in patients or the termination of this study. They were divided into the recurrence group (RG) and the nonrecurrence group (NRG) according to whether the endpoint event occurred. The venous blood of patients was collected at the first diagnosis and subsequent visit (at the time of recurrence or termination of the study) to measure the Ig A and Ig G using a full automatic special protein analyzer and the TNF-α level by enzyme-linked immunosorbent assay. The data obtained in this study were analyzed by univariate analysis to choose the factors with difference in statistical significance to draw the ROC curve, and the areas under the curve (AUC) were recorded to analyze the potential mechanism of Ig A, Ig G, and TNF-α in predicting the recurrence of MM. Results: After follow-up visit, there were 62 patients with recurrence (62.0%) and 38 patients without recurrence (38.0%), with no obvious difference in gender, age, body weight, and immune classification between the two groups (P > 0.05). Compared with the NRG, the levels of soluble interleukin-2 receptor (sIL-2R) and ß 2-microglobulin (ß 2-MG) in the RG at the first diagnosis were distinctly higher (P < 0.001); the levels of Ig A, Ig G, and TNF-α in the RG at the first diagnosis were visibly higher (P < 0.05); and the levels of Ig A, Ig G, and TNF-α in the RG at the subsequent visit were clearly higher (P < 0.05). There was a correlation between Ig G, Ig A, and TNF-α and ß 2-MG at the first diagnosis and the subsequent visit (P < 0.05); there was a correlation between Ig G and TNF-α, and sIL-2R at the first diagnosis and the subsequent visit (P < 0.05); and there was a correlation between Ig A and sIL-2R at the subsequent visit (P < 0.05). The AUC of Ig G, Ig A, and TNF-α in predicting the MM at the first diagnosis were 0.772, 0.776, and 0.778, respectively. Conclusion: The serum Ig A, Ig G, and TNF-α had a predictive value in the recurrence of MM, and TNF-α was correlated with sIL-2R and ß 2-MG, with the highest AUC and the best predictive value.

Influence of demethylation on regulatory T and Th17 cells in myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) represents a heterogeneous hematopoietic disorder in which mature blood cells are derived from an abnormal multipotent progenitor cell. The current therapy for MDS involves repeated cycles of DNA methyltransferase (DNMT) inhibitors, particularly the demethylation drug 5-azacytidine (5-azaC) which has been shown to increase the survival of patients with high-risk MDS. The mechanisms behind the therapeutic effects of 5-azaC are not yet clear. In this study the effect of 5-azaC on the development of regulatory T cells (Tregs) and T-helper 17 (Th17) cells was investigated. The numbers of CD4+ T-cell subsets in 30 patients with intermediate-2/high-risk MDS were serially assessed at diagnosis and following 5-azaC treatment. The number of FoxP3+ Tregs was significantly higher after 3 months of therapy. However, there was no statistical difference in the number of Th17 cells following treatment. In vitro, 5-azaC enhanced the overall proportion of Tregs, but not Th17, in CD4+ T cells from patients with MDS. Addition of 5-azaC reduced the proliferative capacity of Tregs, suggesting that the increase in Tregs was due to conversion of conventional CD25- cells, rather than proliferation of CD25+FoxP3+ cells. The FoxP3 expression in 5-azaC-treated T effectors was also increased. Interestingly, while Tbet and RORγT mRNA transcription had no obvious changes, due to the demethylation of the FoxP3 promoter, these findings are important in associating the induction of DNA hypomethylation and the clinical response to 5-azaC.

[Effect of electronic moxibustion on memory function in patients with amnestic mild cognitive impairment].

OBJECTIVE: To observe the effect of electronic moxibustion on memory function in the patients with amnestic mild cognitive impairment (aMCI). METHODS: A total of 59 aMCI patients were randomized into an electronic moxibustion group (30 cases) and a placebo moxibustion group (29 cases). In the electronic moxibustion group, the electronic moxibustion was applied to Baihui (GV 20), Dazhui (GV 14), Mingmen (GV 4) and Taixi (KI 3), 45 ℃ in temperature, 20 min each time. The treatment was given once a day, 5 times a week. The treatment for 4 weeks was as one course and 2 courses were required totally. In the placebo moxibustion group, the moxa-free patch was used, 38 ℃ in temperature. The acupoint selection and the treatment frequency were same as the electronic moxibustion group. Before and after treatment, Rivermead behavior memory test (RBMT) was adopted to evaluate the global memory function of the patients in the two groups and the N-back task test was adopted to evaluate working memory function separately. Additionally, the mini-mental state examination (MMSE) and its immediate memory, Montreal cognitive assessment (MoCA) and its delay recall were adopted to evaluate the global cognitive function and memory function. RESULTS: In the electronic moxibustion group, after treatment, RBMT score, N-back accuracy rates, MMSE and MoCA scores and the scores of immediate memory and delay recall were improved significantly as compared with those before treatment (P<0.01). In the placebo moxibustion group, the accuracy rates of 1-back and 2-back task and the scores of immediate memory and delay recall were improved obviously as compared with those before treatment (P<0.05, P<0.01). After treatment, the improvements of RBMT score, the accuracy rates of N-back task and MMSE and MoCA scores in the electronic moxibustion group were higher than those in the placebo moxibustion group (P<0.05). CONCLUSION: Electronic moxibustion improves memory function in the patients with amnestic mild cognitive impairment.

Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients.

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong (EX-HN1), Yintang (EX-HN3), Neiguan (PC6), Taixi (KI3), Fenglong (ST40), and Taichong (LR3), or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.

[Distribution of CD45RO⁺ T and CD45RA⁺ T Cells in Peripheral Blood of Patients with Peripheral T Cell Lymphoma].

OBJECTIVE: To investigate the clinical significance of memory T cells (CD45RO⁺ T) and the initial T cells (CD45RA⁺ T) distribution in peripheral blood of patients with peripheral T-cell lymphoma (PTCL). METHODS: A total of 27 patients diagnosed as PTCL in our hospital from February 2010 to February 2014 were collected in this study; whereas 30 healthy people were enrolled as control. The distribution of CD45RO⁺ T and CD45RA⁺ T cells were detected seperately in each group, and the results were analysed further. RESULTS: The expression of T cell antigens in lymphnodes of PTCL patients were diverse: the CD4⁺ T cells were the main immune phenotype, while the B cell-related antigen was not expressed. The CD4⁺/CD8⁺, CD4⁺ CD45RO⁺ T in the peripheral blood of PTCL patients were significantly lower than that in normal group (P < 0.05); while the CD4, CD45RA⁺ T, CD8⁺ CD45RA⁺ T and CD8⁺ CD45RO⁺ T were significantly higher than that in normal group (P < 0.05). The patients in stage I/II had higher CD4⁺/CD8⁺, CD4⁺ CD45RO⁺ T than those in stage III/IV (P < 0.05), whereas the CD4⁺ CD45RA⁺ T, CD8⁺ CD45RA⁺ T and CD8⁺ CD45RO⁺ T were significantly lower than those in the stage III/IV patients (P < 0.05). CONCLUSION: The distributions of CD45RA⁺ T and CD45RO⁺ T in PTCL patients are quite different, and the corresponding treatment might be adopted according to the different distribution of these cells, so as to improve the diagnosis and prognosis of PTCL.