A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections.

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

Micro(nano)plastics in human urine: A surprising contrast between Chongqing's urban and rural regions.

Microplastics (100 nm-5 mm) and nanoplastics (<100 nm) collectively referred to as micro(nano)plastics (MNPs), which are emerging pollutants all over the world. Environmental differences affect its distribution. The content of MNPs differs between urban and rural environments, according to previous studies. To understand the actual situation of human exposure to MNPs in various environments, this study collected 12 urine samples from volunteers in urban and rural regions of Chongqing and used pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and laser direct infrared spectroscopy (LDIR) to detect and analyze MNPs in urine. With an average abundance of 1.50 (2.31) mg/kg, MNPs were found in 9 samples by Py-GC/MS. Polyethylene (PE), polyvinyl chloride (PVC) and polyamide 66 (PA66), three different types of MNPs were found, with PE content being the highest among them. By using LDIR, MNPs were found in 7 samples, with an average abundance of 15.17 (23.13) particles/kg. Five different types of MNPs were found, with acrylates (ACR) being the main type, followed by polymethylmethacrylate (PMMA), polyurethane (PU), polypropylene (PP), polyethylene terephthalate (PET). The findings demonstrated that urban region had much greater levels and more types of MNPs in human urine than rural. Additionally, regular contact with plastic toys and the use of personal care products are linked to the presence of MNPs. The influence of environmental factors on the actual exposure of the human body to MNPs was preliminary explored in this study, and two different methods were used for the first time to simultaneously detect and analyze MNPs in human urine. This allowed for the feasibility of comprehensively and effectively quantitatively analyzing the actual exposure of the human body to MNPs, and also provided the theoretical foundation for further research on the harm of MNPs to human health in different environments.

MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation.

Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of immunoglobulin (Ig)A in maintaining gut homeostasis and preventing inflammation has been well established. Our earlier work demonstrated that the marginal zone and B1 cell-specific protein (MZB1) promotes gut IgA secretion and its absence results in pronounced dextran sulfate sodium salt (DSS)-induced colitis. In the present study, we explored the role of MZB1 in CRC development using the azoxymethane (AOM)/DSS-induced CRC model. We observed an increase in both the number and size of the tumor nodules in Mzb1-/- mice compared with Mzb1+/+ mice. The increase in CRC development and progression in Mzb1-/- mice was associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation. Oral administration of the monoclonal IgA, W27, alleviated both the gut inflammation and AOM/DSS-induced CRC. Notably, cohousing Mzb1+/+ and Mzb1-/- mice from the 10th day after birth led to similar CRC development. Our findings underscore the pivotal role of MZB1-mediated IgA secretion in suppressing the onset and progression of CRC triggered by gut inflammation. Moreover, our study highlights the profound impact of microbiota composition, modulated by gut IgA levels, on gut inflammation. Nonetheless, establishing a direct correlation between the severity of colitis and subsequent CRC development and the presence or absence of a particular microbiota is challenging.

Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome.

Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7 high, TCF7 high, and HLA-DR low) and Treg2 (CCR7 low, TCF7 low, and HLA-DR high). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.

LAPTM5 mediates immature B cell apoptosis and B cell tolerance by regulating the WWP2-PTEN-AKT pathway.

Elimination of autoreactive developing B cells is an important mechanism to prevent autoantibody production. However, how B cell receptor (BCR) signaling triggers apoptosis of immature B cells remains poorly understood. We show that BCR stimulation up-regulates the expression of the lysosomal-associated transmembrane protein 5 (LAPTM5), which in turn triggers apoptosis of immature B cells through two pathways. LAPTM5 causes BCR internalization, resulting in decreased phosphorylation of SYK and ERK. In addition, LAPTM5 targets the E3 ubiquitin ligase WWP2 for lysosomal degradation, resulting in the accumulation of its substrate PTEN. Elevated PTEN levels suppress AKT phosphorylation, leading to increased FOXO1 expression and up-regulation of the cell cycle inhibitor p27Kip1 and the proapoptotic molecule BIM. In vivo, LAPTM5 is involved in the elimination of autoreactive B cells and its deficiency exacerbates autoantibody production. Our results reveal a previously unidentified mechanism that contributes to immature B cell apoptosis and B cell tolerance.

Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy.

Ferroptosis therapy by catalyzing the Fenton reaction has emerged as a promising tumor elimination strategy for lung adenocarcinoma (ADC). However, the unsatisfactory Fenton reaction efficiency, strong intracellular antioxidant system, and insufficient lung drug accumulation limits the ferroptosis therapeutic effect. To address these issues, an inhalable nanoreactor was proposed by spontaneously adsorbing biomimetic protein corona (PC) composed of matrix metalloproteinase 2 responsive gelatin and glutamate (Glu) on the surface of cationic nanostructured lipid carriers (NLC) core loaded with ferrocene (Fc) and fluvastatin. The prepared Fc-NLC(F)@PC could be nebulized into lung lesions with 2.6 times higher drug accumulation and boost lipid peroxide production by 3.2 times to enhance ferroptosis therapy. Mechanically, fluvastatin was proved to inhibit monocarboxylic acid transporter 4 mediated lactate efflux, inducing tumor acidosis to boost Fc-catalyzing reactive oxygen species production, while the extracellular elevating Glu concentration was found to inhibit xCT (system Xc-) functions and further collapse the tumor antioxidant system by glutathione synthesis suppression. Mitochondrial dysfunction and cell membrane damage were involved in the nanoreactor-driven ferroptotic cell death process. The enhanced antitumor effects by combination of tumor acidosis and antioxidant system collapse were confirmed in an orthotopic lung ADC tumor model. Overall, the proposed nanoreactor highlights the pulmonary delivery approach for local lung ADC treatment and underscores the great potential of ferroptosis therapy.

Advances in PSMA-targeted therapy for prostate cancer.

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein located on the cell membrane, is specifically and highly expressed in prostate cancer (PCa). Besides, its expression level is related to tumor invasiveness. As a molecular target of PCa, PSMA has been extensively studied in the past two decades. Currently, a great deal of evidence suggests that significant progresses have been made in the PSMA-targeted therapy of PCa. Herein, different PSMA-targeted therapies for PCa are reviewed, including radioligand therapy (177Lu-PSMA-RLT, 225Ac-PSMA-RLT), antibody-drug conjugates (MLN2704, PSMA-MMAE, MEDI3726), cellular immunotherapy (CAR-T, CAR/NK-92, PSMA-targeted BiTE), photodynamic therapy, imaging-guided surgery (radionuclide-guided surgery, fluorescence-guided surgery, multimodal imaging-guided surgery), and ultrasound-mediated nanobubble destruction.

Single-cell RNA sequencing reveals the molecular features of peripheral blood immune cells in children, adults and centenarians.

Peripheral blood immune cells have different molecular characteristics at different stages of the whole lifespan. Knowledge of circulating immune cell types and states from children to centenarians remains incomplete. We profiled peripheral blood mononuclear cells (PBMCs) of multiple age groups with single-cell RNA sequencing (scRNA-seq), involving the age ranges of 1-12 (G1), 20-30(G2), 30-60(G3), 60-80(G4), and >110 years (G5). The proportion and states of myeloid cells change significantly from G1 to G2. We identified a novel CD8+CCR7+GZMB+ cytotoxic T cell subtype specific in G1, expressing naive and cytotoxic genes, and validated by flow cytometry. CD8+ T cells showed significant changes in the early stage (G1 to G2), while CD4+ T cells changed in the late stage (G4 to G5). Moreover, the intercellular crosstalk among PBMCs in G1 is very dynamic. Susceptibility genes for a variety of autoimmune diseases (AIDs) have different cell-specific expression localization, and the expression of susceptibility genes for AIDs changes with age. Notably, the CD3+ undefined T cells clearly expressed susceptibility genes for multiple AIDs, especially in G3. ETS1 and FLI1, susceptibility genes associated with systemic lupus erythematosus, were differentially expressed in CD4+ and CD8+ effector cells in G1 and G3. These results provided a valuable basis for future research on the unique immune system of the whole lifespan and AIDs.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor.

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

Structural Superiority of Guanidinium-Rich, Four-Armed Copolypeptides: Role of Multiple Peptide-Membrane Interactions in Enhancing Bacterial Membrane Perturbation and Permeability.

The development of novel antimicrobials is a top priority to address the growing epidemic of multidrug-resistant pathogens. Since cationic nonamphiphilic star-shaped antimicrobials are promising molecular scaffolds that provide a high charge density in binding anionic bacterial bilayers, this research aimed to further increase their membrane perturbation capability by introducing guanidinium groups to the antimicrobials via enhancing membrane insertion. In particular, computational simulation and experimental investigations revealed that our designed guanidinium-rich alternating copolypeptide, four-armed poly(arginine-alt-glycine), can interact with both the headgroups and unsaturated tails of phospholipids in bacterial membranes through multiple interactions, including electrostatic, cation-π, and T-shaped π-π interactions, allowing it to penetrate deeper inside the biologically inaccessible high-energy barrier of the hydrophobic lipid bilayer interior to cause membrane permeabilization and precipitation of the bacterial cytoplasm. Furthermore, glycine was observed to have a unique effect in enhancing the performance of arginine-based copolypeptide. Four-armed poly(arginine-alt-glycine) exhibited broad-spectrum antimicrobial activity, high bactericidal efficiency, and negligible hemolysis. The in vivo antibacterial performance of the copolypeptide was superior to that of doxycycline in a mouse model of Pseudomonas aeruginosa skin infection, accompanied by negligible local and systemic toxicity. Our results demonstrate that this guanidinium-rich, nonamphiphilic, star-shaped structure may promote the development of next-generation antimicrobials.

Epidemiological and clinical characteristics analysis of 11 children with 2019 novel coronavirus infection in Chongqing: a single-center retrospective study.

BACKGROUND: The global epidemic of the 2019 novel coronavirus (2019-nCoV) is still going on. This article shares information about the infected children from a treatment center in Chongqing, China. METHODS: A retrospective analysis of the epidemiology, clinical symptoms, signs, laboratory examinations, chest computed tomography results, treatment effect of 11 children infected by 2019-nCoV was performed. Children were diagnosed from January 25 to February 29, 2020 in Chongqing University Three Gorges Hospital. RESULTS: The mean age of the 11 children with 2019-nCoV infection was 11 years and 5 months. Two cases (18%) were imported cases from Wuhan. The 9 cases (82%) were family cluster cases. There were 5 asymptomatic type cases (45%), 2 mild cases (18%), and 4 common type cases (37%). The most common symptom was fever (5 cases), cough (3 cases), sore throat (1 case) and diarrhea (1 case). There were abnormal chest CT changes in 6 cases, including 4 cases with patchy ground-glass opacities and 2 cases with thickened lung texture. Laboratory tests showed that procalcitonin increased in 4 cases (36%), and C-reactive protein (CRP) increased in 1 case (9%). In lymphocyte subgroup examination, lymphocyte count increased in 2 cases (18%) and decreased in 1 case (9%); T%, cluster of differentiation 8 (CD8)+ T%, and natural killer (NK) cell% were normal in 11 cases; CD4+ T% was increased in 2 cases (18%), and CD4+ T%/CD8+ T% was decreased in 1 case (9%); B% was increased in 1 case (9%). The interleukin 4 (IL-4), IL-10, and IL-17 in 11 cases were normal; IL-6 was increased in 7 cases (64%); tumor necrosis factor-alpha (TNF-α) was increased in 1 case (9%); and interferon gamma (IFN-γ) was increased in 6 cases (55%). All patients had been discharged from the hospital. CONCLUSIONS: Children are generally susceptible to 2019-nCoV, and the main way of infection is close contact with an infected person in the family. Clinical symptoms are mild. Laboratory and chest CT examinations are not as typical as those of adults. The prognosis is generally good. The unique immune function of children may help fight the new coronavirus.

The research advances of exosomes in esophageal cancer.

Esophageal carcinoma (EC) is one of the most common human digestive tract tumors, with high morbidity and mortality. It is necessary to elucidate the mechanism of cancer progression and seek early EC diagnostic markers for prompt detection and intervention. Exosomes are membrane nanovesicles secreted from many nucleated cells, 30-100 nm in diameter, containing various proteins, lipids and nucleic acids. They exist in peripheral blood, urine, ascites and other body fluids, widely engaged with intercellular material exchange and signal communication. Exosomes secreted from EC cells or tissues conduct important functions in tumor growth and progression. The detection and analysis of tumor-derived or tumor-associated exosomes has potential for EC early diagnosis and prognosis assessment. In the present paper, the exosomes' biological behaviors, isolation, detection and functions in EC progression - using as potential biomarkers for EC diagnosis or prognosis - are reviewed.

Highly coke resistant Mg-Ni/Al2O3 catalyst prepared via a novel magnesiothermic reduction for methane reforming catalysis with CO2: the unique role of Al-Ni intermetallics.

Addition of alkaline promoters is considered to be an effective way to improve the coking resistance of the metal/support composite catalysts for dry reforming of methane (DRM). The traditional metal/promoter/support composites for DRM catalysis are generally obtained from alkaline species impregnation and then high temperature H2 reduction. This two-step process leads to a random distribution of metal-promoter interaction. We herein report a novel magnesiothermic method to reduce Ni from spinel precursor and introduce alkaline Mg(ii) into the composite at the same time, which also gratifies the interaction between the promoter and metal nanoparticles (NPs). The reaction paths to Mg reduction are proposed. The as prepared catalysts show good activity and outstanding coking resistance in DRM. The Ni-Al intermetallics in the catalyst were found for the first time to play an important role in coking resistance as they can be in situ transformed into Ni nanoparticles and MgAl2O4 with strong metal-support interaction during the DRM.

The Possible Mechanisms of HSV-TK/Hyperthermia Combined with 131I-antiAFPMcAb-GCV Nanospheres to Treat Hepatoma.

Our previous findings showed a good therapeutic effect of the combination of suicide gene HSV-TK, nuclide 131I, and magnetic fluid hyperthermia (MFH) on hepatoma by using magnetic nanoparticles as linkers, far better than any monotherapy involved, with no adverse effects. This combination therapy might be an eligible strategy to treat hepatic cancer. However, it is not clear how the combination regimen took the therapeutic effects. In the current study, to explore the possible mechanisms of radionuclide-gene therapy combined with MFH to treat hepatoma at tissue, cellular, and molecular levels and to provide theoretical and experimental data for its clinical application, we examined the apoptosis induction of the combination therapy and investigated the expression of the proteins related to apoptosis such as survivin, livin, bcl-2, p53, and nucleus protein Ki67 involved in cell proliferation, detected VEGF, and MVD involved in angiogenesis of tumor tissues and analyzed the pathologic changes after treatment. The results showed that the combination therapy significantly induced the hepatoma cell apoptosis. The expression of survivin, VEGF, bcl-2, p53, livin, Ki67, and VEGF proteins and microvascular density (MVD) were all decreased after treatment. The therapeutic mechanisms may be involved in the downregulation of Ki67 expression leading to tumor cell proliferation repression and inhibition of survivin, bcl-2, p53, and livin protein expression inducing tumor cell apoptosis, negatively regulating VEGF protein expression, and reducing vascular endothelial cells, which results in tumor angiogenesis inhibition and microvascular density decrease and tumor cell necrosis. These findings offer another basic data support and theoretical foundation for the clinical application of the combination therapy.

Hypoxia decrease expression of cartilage oligomeric matrix protein to promote phenotype switching of pulmonary arterial smooth muscle cells.

Extracellular matrix proteins play important roles in the development of pulmonary hypertension(pH). However, the role of Cartilage oligomeric matrix protein (COMP) in the development of hypoxia-induced pH is largely unknown. We tested the hypothesis that COMP deficiency induced by hypoxia leads to the phenotype switching of pulmonary arterial smooth muscle cells (PASMCs). The expression of COMP decreased in a chronic hypoxia rat pH model (P<0.05) and in PASMCs under hypoxia (3%O2) (P<0.05). The expressions of differentiated marker proteins reduced in the pulmonary arteries from 5 month old COMP-/- mice and in PASMCs under hypoxia or with the siRNA of COMP treatment under normoxia, but increased in PASMCs with adenovirus-increased COMP under hypoxia. The absorbance of cell counting kit-8 at 450nm and the expressions of proliferating cell nuclear antigen (PCNA) and osteopontin increased in PASMCs with the siRNA of COMP under normoxia (P<0.05). PCNA and osteopontin decreased in PASMCs with adenovirus-increased COMP under hypoxia (P<0.05). Additionally, the expression of bone morphogenetic protein receptor 2 (BMPR2) was reduced in COMP-/- mice (P<0.01). Both mRNA and protein levels of bone morphogenetic protein 2 (BMP2) were lower in PASMCs with the siRNA of COMP (P<0.05). The protein level of BMP2 could be reversed by adenovirus-increased COMP under hypoxia (P<0.05). These data suggest that COMP could normally have a protective role against PASMC phenotype switching and maintain BMP2/BMPR2 signaling, and these protective actions could be lost as a result of hypoxia promoting a depletion of COMP.

Effect of P2X4R on airway inflammation and airway remodeling in allergic airway challenge in mice.

P2X4 receptor (P2X4R) is the most widely expressed subtype of the P2XRs in the purinergic receptor family. Adenosine triphosphate (ATP), a ligand for this receptor, has been implicated in the pathogenesis of asthma. ATP­P2X4R signaling is involved in pulmonary vascular remodeling, and in the proliferation and differentiation of airway and alveolar epithelial cell lines. However, the role of P2X4R in asthma remains to be elucidated. This aim of the present study was to investigate the effects of P2X4R in a murine experimental asthma model. The asthmatic model was established by the inhalation of ovalbumin (OVA) in BALB/c mice. The mice were treated with P2X4R­specific agonists and antagonists to investigate the role of this receptor in vivo. Pathological changes in the bronchi and lung tissues were examined using hematoxylin and eosin staining, Masson's trichrome staining and Alcian blue staining. The inflammatory cells in the bronchoalveolar lavage fluid were counted, and the expression levels of P2X4R, α­smooth muscle actin (α­SMA) and proliferating cell nuclear antigen (PCNA) were detected using western blotting. In the OVA­challenged mice, inflammation, infiltration, collagen deposition, mucus production, and the expression levels of P2X4R and PCNA were all increased; however, the expression of α­SMA was decreased, compared with the mice in the control group. Whereas treatment with the P2X4R agonist, ATP, enhanced the allergic reaction, treatment with the P2X4R antagonist, 5­BDBD, attenuated the allergic reaction. The results suggested that ATP­P2X4R signaling may not only contribute to airway inflammation, but it may also contribute to airway remodeling in allergic asthma in mice.

[Clinical significance of bone marrow morphological examination and tumor marker detection for lymphoma diagnosis and prognosis].

OBJECTIVE: This study was aimed to evaluate the significance of bone marrow(BM) morphological examination and many tumor marker(TM) detection, especially carcinoembryonic antigen (CEA), cancer antigen 125(CA125), cancer antigen 15-3 (CA15-3) and serum ferritin (SF) for lymphoma diagnosis and prognosis. METHODS: A total of 47 confirmed patients with lymphoma in our hospital from January 2012 to October 2013 and 20 health peoplels as normal controls were performed with bone marrow morphological examination, at the same time, the electrochemistry luminescent technique was applied for detecting levels of TM (especially CEA, CA125, CA15-3 and SF) in serum samples of lymphoma patient and normal controls, then the BM immature lymphocyte counts of these people and clinical parameters were analyzed for diagnosis and prognosis. RESULTS: There was significant differences in all the four TM levels between serum samples of lymphoma patients and normal control (P=0.029, P=0.000, P=0.005, P=0.000). These TM levels had no correlation with age, sex white blood cell, lymphocyte, platelet counts and anemia of lymphoma patients (P>0.05). It was also found that the patients with elevated TM levels had high BM immature lymphocytes (lymphoma cells) counts, B symptoms, advanced clinical stage and high IPI index (P<0.05). The CA15-3 and SF levels in serum samples of lymphoma patients with BM infiltration were higher than that in lymphoma patients without BM infiltration (P=0.002, P=0.000). CONCLUSION: Combination of BM morphological examination with serum TM level detection plays an important role in diagnosis, clinical stage and prognosis evaluation of lymphoma patients. It is also very important for assessing BM infiltration status of lymphoma patients.