[Research advances in the etiology and pathogenesis of immunoglobulin A vasculitis]. / å ç–«çƒè›‹ç™½Aè¡€ç®¡ç‚Žç— å› åŠå‘ç— æœºåˆ¶çš„ç ”ç©¶è¿›å±•.

Immunoglobulin A vasculitis (IgAV), also known as Henoch-Schönlein purpura, has complex etiology and pathogenesis which have not been fully clarified. The latest research shows that SARS-CoV-2 and related vaccines, human papilloma vaccine, and certain biological agents can also induce IgAV. Most studies believe that the formation of galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complex plays a crucial role in the pathogenesis of IgAV. It is hypothesized that the pathogenesis of IgAV is associated with the binding of IgA1 to anti-endothelial cell antibodies. In addition, genetics also constitutes a major focus of IgAV research. This article reviews the new advances in the etiology of IgAV and summarizes the role of Gd-IgA1, Gd-IgA1-containing immune complex, anti-endothelial antibody, IgA1 conjugates, T lymphocyte immunity, and genetic factors in the pathogenesis of IgAV.

[Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism].

OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1ß, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION: Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

[Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice].

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION: Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Genotype-phenotype correlation in Chinese patients with dystrophic epidermolysis bullosa pruriginosa.

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare variant of dystrophic epidermolysis bullosa (DEB) due to dominant or recessive mutations in the COL7A1 gene. More than 40 mutations in COL7A1 have been described in DEB-Pr. The aim of this study was to understand the genotype-phenotype correlation in Chinese patients with DEB-Pr. Three Chinese families with typical clinical features of DEB-Pr were studied. The results were analysed in association with the eight Chinese DEB-Pr patients reported in the literature. In the three Chinese families with DEB-Pr, we found two dominant cases with G1773R and c.6900+1G>C mutations, and one case with heterozygous G2701W mutation of uncertain inheritance mode. In the 10 Chinese patients with dominant type of DEB-Pr, 7 glycine substitutions and three splicing site mutations of exon 87 skipping were identified. Glycine substitution mutations in the triple helix region and exon 87 skipping, leading to the in-frame deletion of 23 amino acid residues in the triple-helix, are often seen in Chinese patients with dominant DEB-Pr, although the glycine substitutions are also frequently present in dominant DEB.

[Detection of serum desmoglein antibody level using enzyme-linked immunosorbent assay (ELISA) for monitoring disease activity in patients with pemphigus vulgaris].

OBJECTIVE: Pemphigus is an autoimmune blistering disease of skin and mucous membranes. Pemphigus vulgaris (PV) is a major subtype of pemphigus, which is histologically characterized by suprabasal acantholysis. The major antigen in PV is desmosomal glycoproteins desmoglein (Dsg) 3. The autoantibodies against Dsg3 cause loss of adhesion between keratinocytes. Some PV patients also have circulating anti-Dsg1 autoantibodies. Enzyme-linked immunosorbent assays (ELISAs) with recombinant Dsg3 and Dsg1 are highly sensitive and specific for detecting anti-Dsg3 and anti-Dsg1 autoantibodies in PV patients. To evaluate the role of desmosomal glycoproteins desmoglein (Dsg3) ELISA and Dsg1 ELISA for detecting anti-Dsg3 and anti-Dsg1 autoantibodies in monitoring disease activity in Pemphigus vulgaris patients. METHODS: Twenty PV patients with long-term follow-up were included. We tested their serial sera with modified Dsg3 ELISA (MESACUP Desmoglein TEST "Dsg3", Medical & Biological Laboratories Co. LTD.), Dsg1 ELISA(MESACUP Desmoglein TEST "Dsg1", Medical & Biological Laboratories Co. LTD.) and indirect immunofluorescence (IIF). Then we analyzed the correlation between Dsg3 ELISA index values, Dsg1 ELISA index values, IIF titres and disease activity scores (ABSIS) along the time course. RESULTS: There were significant correlations between Dsg3 ELISA index values, Dsg1 ELISA index values, IIF titres and disease activity scores (both skin scores and oral scores) (P<0.01) along the time course. Significant differences of Dsg3 ELISA index values, Dsg1 ELISA index values and IIF titres between active time-point group and clinical remission time-point group were also observed (P<0.01). We found that Dsg3 ELISA index values, Dsg1 ELISA index values and IIF titres fluctuated in parallel with disease activity, and ELISA index values were superior to IIF titres. CONCLUSION: Dsg3 ELISA index values fluctuating in parallel with disease activity are useful to monitor disease activity, predict flares or relapses and plan the schedules for tapering the drugs.

A novel selenium and copper-containing peptide with both superoxide dismutase and glutathione peroxidase activities.

Superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) play crucial roles in balancing the production and decomposition of reactive oxygen species (ROS) in living organisms. These enzymes act cooperatively and synergistically to scavenge ROS. In order to imitate the synergism of these enzymes, we designed and synthesized a novel 32-mer peptide (32P) on the basis of the previous 15-mer peptide with GPX activity and a 17-mer peptide with SOD activity. Upon the selenation and chelation of copper, the 32-mer peptide is converted to a new Se- and Cu-containing 32-mer peptide (Se-Cu-32P) and displays both SOD and GPX activities and its kinetics was studied. Moreover, the novel peptide was demonstrated to be able to better protect vero cells from the injury induced by xanthine oxidase (XOD)/xanthine/Fe2+ damage system than its parents. Thus, this bifunctional enzyme imitated the synergism of SOD and GPX and could be a better candidate of therapeutic medicine.

[Induction of prostate cancer-specific CTLs with dendritic cells pulsed by different types of tumor antigens].

OBJECTIVE: To study the effectiveness of freeze-thaw antigens and acid eluted peptide antigens extracted from tumor cell-pulsed dendritic cells (DC) in inducing prostate cancer-specific cytotoxic T lymphocytes (CTL) in vitro. METHODS: Tumor antigens were extracted from the prostate cancer cell line PC-3 with the repeated freeze-thaw and weak acid elution methods. Peripheral blood mononuclear cells were cultured with recombinant human GM-CSF and IL-4 for inducing DCs in vitro. Then the DCs were pulsed with the two kinds of prostate cancer tumor antigens respectively and cultured with T cells for inducing CTLs. The activity of the tumor-specific CTLs were detected by LDH release assay. RESULTS: The protein content in the tumor antigens obtained from PC-3 (2 x 10(7)) by citric acid-phosphate buffer elution and that by the repeated freeze-thaw method were (212.2 +/- 7.9) microg and (963.0 +/- 25.3) microg, respectively. The two kinds of prostate cancer antigens-pulsed DCs had a significant role in inducing the PC-3 cell-specific CTLs, and the CTLs induced by acid-eluted peptide antigen-pulsed DCs exhibited an even more significant tumor-specific cytotoxicity than those induced by repeated freeze-thaw ([60.4 +/- 5.52]% vs. [43.7 +/- 4.11]%, P < 0.01). CONCLUSION: Both the weak acid elution and repeated freeze-thaw methods for extracting prostate cancer antigens can be used for in vitro sensitization of DCs. The DCs pulsed by either of the two kinds of antigens can activate CTLs, and the antigens extracted by weak acid elution are even more effective.

[Curative Efficacy and Survival Analysis of Low-Intensity Traditional Chemotherapy Regimen in the Elderly Patients with Acute Myeloid Leukemia (non-M3)].

OBJECTIVE: To investigate the short-term and long-term curative efficacy of low-intensity traditional chemotherapy regimen for elderly patients with acute myeloid leukemia (AML, non-M3) and related adverse reactions, in order to explore whether low-intensity traditional chemotherapy regimen still has application value in the treatment of elderly AML patients today. METHODS: The clinical characteristics, treatment response and prognosis of 67 elderly patients with AML (non-M3) admitted to our hospital from June 2008 to December 2018 were retrospectively analyzed. All patients received low-intensity conventional chemotherapy (i.e. lower standard dose, and without new drugs listed in China since the 21st century), including DA, HA, CAG, etc. The CR rate, median survival time and 5-year cumulative survival rate of patients were evaluated, and the related indexes were compared with the data reported in domestic and foreign literatures at the same time. RESULTS: The CR rate was 55.2% (37/67), the median survival time was 13.7 months, and the 5-year cumulative survival rate was (24.4±6.3)% in patients received low-intensity tradional chemotherapeutic regimens. The CR rates of high-risk group and non-high-risk group were 38.7% (12/31) and 69.4% (25/36), respectively; the median survival time of high-risk group and non-high-risk group was 8.9 months and 25.2 months respectively; the 5-year cumulative survival rate of high-risk group was (10.2±6.6)% and that of non-high-risk group was (36.0± 9.4)%. Compared with the data reported in the literature at the same time, the data obtained from the low-intensity traditional chemotherapy regimen for the elderly AML did not have an obvious disadvantage, morever had relatively short bone marrow suppression time, low induction early mortality rate and low incidence of severe infection. CONCLUSION: At present, the low-intensity traditional chemotherapy regimen still has good curative effect and survival advantages for elderly AML patients, especially for non-high-risk patients. The adverse reactions are controllable, and the physical and economic conditions of the vast majority of patients can bear the treatment regimen.

Two new compounds from the dried tender stems of Cinnamomum cassia.

Two new compounds, cinnamic aldehyde cyclic d-galactitol 3'R,4'S-acetal (1) and cinnamomumolide (2), along with six known compounds, syringaresinol (3), lyoniresinol (4), 5,7,3'-trimethoxyl-( - )-epicatechin (5), 5,7-dimethoxyl-3',4'-di-O-methylene-( +/- )-epicatechin (6), 2-methoxyl-4-hydroxy cinnamyl aldehyde (7), and glucosyringic acid (8), have been isolated from the dried tender stems of Cinnamomum cassia. Their structures were elucidated based on spectroscopic data. Compound 2 was elucidated as 8-methoxyl-9-hydroxy-3',4'-methylenedioxy-3S,4R-diphenyl butyrolactone, named cinnamomumolide, which exhibited activity in protecting against the injury caused by hydrogen peroxide oxidation on human umbilical vein endothelial cells, with an EC(50) value of 10.7 microM. Compounds 3-8 were isolated from the title plant for the first time.

[Basic and clinical research on paraneoplastic pemphigus].

Paraneoplastic pemphigus (PNP) is an autoimmune blistering skin disease associated with neoplasms. Clinically, it is characterized by severe mucosal erosions and various cutaneous lesions. Suprabasal acantholysis and cleft with scattered necrotic keratinocytes are the unique histopathological features of PNP. The pathogenic autoantibodies existed in PNP sera, and their production was correlated with the associated tumor. Early detection and resection of the tumor are essential for the treatment of the disease.

[Surgical treatment and prognosis analysis of localized retroperitoneal Castleman disease: a study of 20 cases].

OBJECTIVE: To investigate the clinical characteristics, surgical treatment and prognosis analysis of localized retroperitoneal Castleman disease (CD), and to improve the level of diagnosis and treatment of retroperitoneal Castleman disease with paraneoplastic pemphigus (PNP). METHODS: The clinical data of retroperitoneal CD with PNP from January 1993 to May 2009 were compared with CD without PNP retrospectively, including clinical features, tumor site, lab examination, surgical treatment, pathologic subtype and results of surgery. RESULTS: (1) Retroperitoneal Castleman disease more likely originated in para-kidney and iliac fossa with middle age of 36 years old, especially in left retroperitoneum. Of the 20 cases, 18 tumors (90%) were hyaline vascular variants and 2 were mixed variants. There was no statistical difference in gender, age, tumor site and pathological subtype between two groups. (2) Retroperitoneal CD with PNP more likely complicated with bronchiolitis obliterans (BO) and high level of serum CEA/CA242. (3) Retroperitoneal Castleman tumors had clear margin, intact envelop and were easily resectable, however the biological behavior of CD with PNP might tend malignant changing, invade adjacent blood vessel or seed locally, and eventually relapse after operation. (4) The 5-year survival rate of retroperitoneal CD with PNP was 42.8%, significantly lower than those without PNP. The average survival time was 30 months. Bronchiolitis obliterans and radical resection were the key effect in prognosis of retroperitoneal CD. CONCLUSIONS: Retroperitoneal CD with PNP has distinctive clinical features. Early diagnosis, prompt removal of tumor and termination secretion of causative antibody are critical to the management of this disease.

Ni(ii)-doped anionic metal-organic framework nanowire arrays for enhancing the oxygen evolution reaction.

Herein, an anionic metal-organic framework nanowire array not only directly grew on Cu foam, but also captured Ni(ii) ions at an ultra-small particle level. The hybrid material exhibited high activity with low overpotential (310 mV at 20 mA cm-2 in 1.0 M KOH solution) toward the oxygen evolution reaction (OER) (1 M KOH), with performance comparable to that of the precious metal benchmark. These findings may expand the field of MOFs for scaled-up water electrolysis.

Tumor-released autophagosomes induces CD4+ T cell-mediated immunosuppression via a TLR2-IL-6 cascade.

BACKGROUND: CD4+ T cells are critical effectors of anti-tumor immunity, but how tumor cells influence CD4+ T cell effector function is not fully understood. Tumor cell-released autophagosomes (TRAPs) are being recognized as critical modulators of host anti-tumor immunity during tumor progression. Here, we explored the mechanistic aspects of TRAPs in the modulation of CD4+ T cells in the tumor microenvironment. METHODS: TRAPs isolated from tumor cell lines and pleural effusions or ascites of cancer patients were incubated with CD4+ T cells to examine the function and mechanism of TRAPs in CD4+ T cell differentiation and function. TRAPs-elicited CD4+ T cells were tested for their suppression of effector T cell function, induction of regulatory B cells, and promotion of tumorigenesis and metastasis in a mouse model. RESULTS: Heat shock protein 90α (HSP90α) on the surface of TRAPs from malignant effusions of cancer patients and tumor cell lines stimulated CD4+ T cell production of IL-6 via a TLR2-MyD88-NF-κB signal cascade. TRAPs-induced autocrine IL-6 further promoted CD4+ T cells secretion of IL-10 and IL-21 via STAT3. Notably, TRAPs-elicited CD4+ T cells inhibited CD4+ and CD8+ effector T cell function in an IL-6- and IL-10-dependent manner and induced IL-10-producing regulatory B cells (Bregs) via IL-6, IL-10 and IL-21, thereby promoting tumor growth and metastasis. Consistently, inhibition of tumor autophagosome formation or IL-6 secretion by CD4+ T cells markedly retarded tumor growth. Furthermore, B cell or CD4+ T cell depletion impeded tumor growth by increasing effector T cell function. CONCLUSIONS: HSP90α on the surface of TRAPs programs the immunosuppressive functions of CD4+ T cells to promote tumor growth and metastasis. TRAPs or their membrane-bound HSP90α represent important therapeutic targets to reverse cancer-associated immunosuppression and improve immunotherapy.

Ni(ii)-based coordination polymers for efficient electrocatalytic oxygen evolution reaction.

The exploration of highly efficient, stable and cheap water oxidation electrocatalysts using earth-abundant elements is still a great challenge. Herein, alkaline-stable cationic Ni(ii) coordination polymers (Ni-CPs) were successfully obtained under hydrothermal conditions, which could stabilize the incorporation of Fe(iii) to form Fe-immobilized Fe@Ni-CPs. The newly developed Ni-based CPs were used for the first time as an effective electrocatalyst for the oxygen evolution reaction in strong alkaline media.

BF211, a derivative of bufalin, enhances the cytocidal effects in multiple myeloma cells by inhibiting the IL-6/JAK2/STAT3 pathway.

Despite remarkable advances in multiple myeloma (MM) therapy, this condition remains incurable. BF211 is an active compound derived from bufalin, which is isolated from the Traditional Chinese Medicine, Chansu. In this study, we explored the cytotoxicity of BF211 in 20 tumor cell lines and discovered that the MM cell lines, ARP-1 and CAG, exhibited greater sensitivity to BF211. Compared with bufalin, BF211 induced a greater apoptotic effect and lower acute toxicity at nanomolar concentration. The IL-6/JAK2/STAT3 signaling pathway is essential to the progression and development of MM. We showed that exogenous IL-6 promoted MM cell proliferation in a dose-dependent manner and this effect was blocked by BF211. Furthermore, BF211 suppressed the phosphorylation of JAK2 and STAT3 both in vivo and in vitro. In a mouse MM xenograft model, BF211 significantly inhibited tumor growth and did not affect body weight. In conclusion, the anti-MM activity of BF211 is mediated mainly by suppressing the IL-6/JAK2/STAT3 signaling pathway. Thus, we suggest that BF211 warrants further investigation in clinical trials in MM.

Tumor cell-released autophagosomes (TRAP) enhance apoptosis and immunosuppressive functions of neutrophils.

Our previous studies have confirmed that tumor cell-released autophagosomes (TRAP) could induce the differentiation of B cells into IL-10+ regulatory B cells (Bregs) with suppressive activities on T lymphocytes. However, the mechanism of TRAP-mediated immune suppression is still largely unclear. Herein, we sought to assess the immunomodulatory effect of TRAPs on human neutrophils, a major immune cell type that infiltrates human tumor tissues. We found that TRAPs enriched from malignant effusions or ascites of cancer patients and tumor cell lines were rapidly and effectively phagocytized by neutrophils through macropinocytosis and promoted neutrophil apoptosis via reactive oxygen species (ROS) generation and caspase-3 activation. Moreover, the apoptotic neutrophils that have phagocytized TRAPs inhibited the proliferation and activation of CD4+ T and CD8+ T cells in a cell contact- and ROS-dependent manner. These findings define a novel TRAP-mediated mechanism in neutrophils that potentially suppresses the anti-tumor T cell immunity and highlight TRAPs as an important target for future tumor immunotherapy.

[Effect of topical tacrolimus ointment on expression of Toll-like receptors 2 and 4 in lesional atopic dermatitis skin].

OBJECTIVE: To investigate the role of Toll-like receptor(TLR) 2 and TLR4 in pathogenesis of atopic dermatitis(AD) and the effect of topical tacrolimus ointment on expression of TLR2 and TLR4 in lesional AD skin. METHODS: Immunohistochemistry was employed to study the expression of TLR2 and TLR4 in normal skin and lesional AD skin before and after using topical tacrolimus ointment. RESULTS: The basal keratinocytes in normal skin constitutively expressed TLR2 and TLR4. In contrast, lesional epidermis from 9 patients with acute AD overexpressed TLR2 and TLR4 on the whole epidermis keratinocytes with membranous and cytoplasmic staining pattern. After using topical tacrolimus ointment for three weeks, TLR2 and TLR4 were expressed on basal and suprabasal keratinocytes with membranous and cytoplasmic staining pattern. CONCLUSION: These data suggest that TLR2 and TLR4 expressed by epidermal keratinocytes constitute part of the innate immune system of the skin, and increased TLR2 and TLR4 expression may be related to the skin innate immuno-inflammatory response in atopic dermatitis. Topical tacrolimus may directly or indirectly inhibit or down-regulate TLR2 and TLR4 expression in KC and inhibit skin innate immuno-inflammatory response related to TLR-NFkappaB signal transduction and regulation in atopic dermatitis.

[Design, synthesis and insulin-sensitizing activity of some peroxisome proliferator-activated gamma agonists].

AIM: To find new peroxisome proliferator-activated y agonists with high activity and low toxicity. METHODS: Based on JTT-501 and JTT-20993, new isoxazolidine-3,5-dione and noncyclic 1,3-dicarbonyl compounds were designed and synthesized. Their insulin-sensitizing activities were evaluated. RESULTS: Eight new compounds were obtained. The structures of synthesized compounds were characterized by NMR, MS and IR. Four compounds (1A-4A) showed insulin-sensitizing activities. CONCLUSION: Compounds (1A and 3A) showed excellent insulin-sensitizing activities and should be worth further investigation.

Progression of Large Lymphoma Is Significantly Impeded with a Combination of Gemcitabine Chemotherapy and Dendritic Cells Intra-Tumor Vaccination.

Relapsed, refractory lymphoma remains to be a challenge and lacks efficient treatment. Some tumor cells escape from treatment, become resistant to chemotherapeutic agents, and rapidly regenerate into large tumors. Lymphoma cells induce accumulation of Gr-1(+-)CD11b(+) myeloid derived suppressor cells (MDSCs) in lymphatic organs and their vicinity. MDSCs enable tumor cells to escape from immune cells mediated surveillance and attack. Gemcitabine is a chemotherapeutic agent that eliminates both tumor cells and MDSCs, improving the immune environment favorable for subsequent treatment. We evaluated the effects of low dose gemcitabine combined with intra-tumorally delivered dendritic cells (DCs) for the treatment of A20 large-size lymphoma. We showed that MDSCs increased markedly in lymphoma-bearing mice, and that gemcitabine significantly increased the apoptosis of MDSCs. Treatment of lymphoma with either gemcitabine or intra-tumoral DCs alone could not inhibit tumor growth or rescue lymphoma-bearing mice. Treatment of lymphoma with small dose gemcitabine followed by intra-tumorally injected DCs significantly improved the efficacy of either individual treatment by reducing MDSCs, inducing onsite DCs maturation, eliminating tumor cells, inhibiting tumor growth and relapse, and extending the survival of the lymphoma-bearing mice, partly through the induction of the IFNγ secreting cells and the activation of cytotoxic lymphocytes. We showed that NK cells and CD8(+ )T cells were the major effectors to mediate the inhibition of tumor growth. Thus, the observation that gemcitabine synergizes DCs mediated immunotherapy to improve the efficacy of large size lymphoma treatment provides an experimental basis for the combination of chemotherapy and immunotherapy for the efficient treatment of relapsed or refractory lymphoma.

Identification of a novel mutation and a de novo mutation in DKC1 in two Chinese pedigrees with Dyskeratosis congenita.

Dyskeratosis congenita (DKC) is a rare and fatal congenital syndrome characterized by the triad of reticular skin pigmentation, nail dystrophy and mucosal leukoplakia, and the predisposition to bone marrow failure and malignancies. Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita. Here we report mutation analysis of two Chinese pedigrees with dyskeratosis congenita. The 15 coding exons of DKC1 and their flanking regions were amplified from genomic DNA by PCR. DNA sequencing and restriction endonuclease digestion were used for mutation detection. Transition mutation of 1226C-->T (P409L) found in the first pedigree is a novel mutation. In the second pedigree, the proband's mother phenotypically normal carried a de novo transition mutation of 1058C-->T (A353 V) in one allele, and transmitted the mutant allele to her two sons who had typical manifestations of dyskeratosis congenita.