[Clinical and biological features and prognosis of patients with leukemic non-nodal mantle cell lymphoma].

Objective: To investigate the clinical, biological and prognostic characteristics of leukemic non-nodal mantle cell lymphoma (nnMCL). Methods: The clinical data of 14 patients with nnMCL and 238 patients with classical mantle cell lymphoma (cMCL) in Blood Diseases Hospital, Chinese Academy of Medical Sciences from November 2000 to October 2020 were retrospectively analyzed. Among the 14 patients with nnMCL, there were 9 males and 5 females, with the age [M (Q1, Q3)] of 57.5 (52.3, 67.0) years. Among the 238 patients with cMCL, there were 187 males and 51 females, with the age of 58.0 (51.0, 65.3) years. The clinical and biological characteristics of the two groups were recorded and compared. Follow-up and efficacy evaluation were conducted by re-examination during hospital stay and telephone follow-up and so on. Results: The proportion of CD200 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [14.6% (19/130)] (P=0.001). The proportion of CD23 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [13.5% (23/171)] (P<0.001). The proportion of CD5 expression in nnMCL patients was 10/14, which was lower than that in cMCL patients [97.4% (184/189)] (P=0.001). The proportion of CD38 expression in nnMCL patients was 4/14, which was lower than that in cMCL patients [69.6% (112/161)] (P=0.005). The expression proportion of sex-determining region of Y chromosome-related high-mobility-group box 11 (SOX11) in nnMCL patients was 1/5, which was lower than that in cMCL patients [77.9% (60/77)] (P=0.014). The proportion of immunoglobulin heavy chain variable region (IGHV) mutations in nnMCL patients was 11/11, which was higher than that in cMCL patients [26.0% (13/50)] (P<0.001). As of April 11, 2021, the follow-up time for nnMCL and cMCL patients was 31 (8-89) months and 48 (0-195) months, respectively. Among the 14 nnMCL patients, 6 patients were still under observation, and 8 patients were treated. The overall response rate (ORR) was 8/8, including 4 patients with complete remission and 4 patients with partial response. The median overall survival and median progression-free survival were not reached in nnMCL patients. In the cMCL group, 50.0% (112/224) patients achieved a complete response, 24.6% (55/224) patients achieved a partial response, and ORR was 74.6% (167/224). There was no statistically significant difference in ORR between the two groups (P=0.205). Conclusions: nnMCL patients have an indolent progression, with higher expression rates of CD23 and CD200 and lower expression rates of SOX11, CD5 and CD38. Most patients have IGHV mutations, with a relatively good prognosis, and"watch and wait"approach is an optional treatment.

[Large B-cell lymphoma with IRF4 rearrangement: six case reports and a literature review].

Objective: To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed. Results: ①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity (n=five cases) and no starry sky pattern (n=6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions: LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity's pathogenesis, treatment options, and long-term prognosis still need to be explored further.

[Clinical and biological characteristics of non-IgM lymphoplasmacytic lymphoma].

Objective: The study aims to explore the clinical and biological characteristics of patients with non-IgM lymphoplasmacytic lymphoma (LPL) . Methods: The clinical data of 340 patients with LPL admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were collected retrospectively, including 23 cases of the non-IgM LPL and 317 cases of the Waldenström's macroglobulinemia (WM) , from July 1993 to August 2020. The clinical and biological characteristics of the two groups were compared. Results: Among 23 patients with the non-IgM type LPL, two patients secreted monoclonal IgA, 14 patients secreted monoclonal IgG, and seven patients did not secrete monoclonal immunoglobulin. The median age of the non-IgM LPL and WM were both 62 (35-81) years old. Compared with the WM group, the proportion of women (56.5% vs 27.3%, P=0.007) , the proportion of splenomegaly (60.1% vs 43.8%, P=0.100) , and the proportion of extranodal invasion (21.7% vs 12.3%, P=0.672) in non-IgM LPL group were higher. Eighteen patients were tested for MYD88 gene mutation, and the overall mutation rate of MYD88 was 55.6%. In the non-IgM LPL group, a total of 17 patients received treatment, which had a comparable proportion (94.4% vs 92.7%, P=0.488) to the WM group. Sixteen patients were evaluated for efficacy, and the overall remission rate of the first-line treatment was 87.5%. The median follow-up time was 33.9 (3.5-125.1) months, and the median PFS and OS were both not reached. The 3-year PFS and OS rates were 71.4% and 68.9%, respectively. In the WM group, the median PFS was 66.2 months and the median OS was 78.1 months. Compared with the WM group, in the non-IgM group no significant differences in PFS (P=0.340) and OS (P=0.544) were seen. Conclusion: The clinical and biological characteristics of the non-IgM LPL and WM patients were similar. However, the proportion of women and extranodal involvement were higher in the non-IgM LPL group. The survival and prognosis of the non-IgM LPL patients were similar to those of the WM patients.

[The prognostic significance of POD24 in 106 cases with splenic marginal lymphoma with bone marrow invasion].

Objective: To explore the effect of progression of disease within 24 months (POD24) on overall survival (OS) of splenic marginal lymphoma (SMZL) with bone marrow invasion, and to compare the clinical characteristics between POD24 SMZL with non-POD24 SMZL patients. Methods: The SMZL patients with bone marrow invasions were retrospectively analyzed between January 2002 and January 2017 treated in our institute, and the patients with sufficient follow-up time to judge POD24 were evaluated the clinical characteristics and prognosis, patients who died of non-progressive factors were excluded. Results: 106 patients were enrolled with a median age of 57 (25-79) years old. ①Clinical characteristics: All patients presented with bone marrow invasion and splenomegaly, 59.4% (63/106) with huge spleen, 14.8% (15/101) with hepatomegaly. Complex karyotype were found in 22.7% (18/79) patients; 13q deletion, 11q (ATM) deletion, 17p (TP53) deletion, and CEP12 abnormality patients presented with the percentage of 5.1% (4/78) , 1.3% (1/72) , 2.5% (2/80) , and 7.5% (4/53) , respectively.②Survival analysis: Univariate analysis showed that POD24, HGB less than 100 g/L and FISH detection of trisomy 12 were poor prognostic factors of OS. Multivariate analysis showed that only POD24 had independent prognostic significance[HR=20.116 (95%CI 2.226-181.820) , P=0.008]. ③Subgroup features: Patients with POD24 had significantly higher rates of mediastinal lymphadenopathy (63.6%vs 18.9%, P=0.005) and complex karyotype (50.0%vs 17.9%, P=0.024) than those without POD24. While the incidence of abdominal lymphadenopathy, anemia, thrombocytopenia, the lower albumin, and the increasing lactate dehydrogenase were higher in POD24 patients, but with no statistically difference. Conclusion: POD24 is an independent prognostic factor of the OS in SMZL. SMZL patients with mediastinal lymphadenopathy and complex karyotypes when diagnosed have a higher risk of POD24.

S doped NiCo2O4 nanosheet arrays by Ar plasma: An efficient and bifunctional electrode for overall water splitting.

Transition metal oxides show great potential as electrocatalysts, owing to the low cost and rich chemical states. However, the limited surface areas, low intrinsic activity and poor hydrogen evolution reaction (HER) activity greatly restrict the application for overall water splitting. Herein, we have constructed S doped NiCo2O4 nanosheet arrays by Ar plasma (Ar-NiCo2O4|S) to enhance active sites and boost catalytic kinetics. Consequently, the Ar-NiCo2O4|S shows the improved performances for HER and oxygen evolution reaction (OER). Further, as bifunctional electrocatalysts, Ar-NiCo2O4|S exhibit a voltage of 1.63 V at 10 mA cm-2, as well as good stability.

Comprehensive unmet needs and correlations with quality of life in Chinese cancer patients.

Increasing evidence indicates unmet supportive need as a detrimental effect on patients' well-being. However, the unmet needs and correlations with quality of life (QOL) in mainland Chinese cancer patients remain unclear. This study aimed to assess the unmet needs and QOL in Chinese cancer patients, and further explore the influencing factors. A cross-sectional descriptive study design was applied. Using a convenience sampling method, 300 cancer patients, including 176 females and 124 males were recruited from five tertiary hospitals in Xi'an city during April to July 2015. Self-administered questionnaires including general information, Comprehensive Needs Assessment Tool (CNAT) and the 36-item Short-Form Health Survey (SF-36) were used for data collection. The mean age of the participants was 52.96 ± 13.45 years. The total score of CNAT was 46.37 ± 21.87, and the most unmet comprehensive needs were healthcare staff, information and health facilities and services domain. The total score of QOL was 48.95 ± 18.80 and 50.35 ± 19.77 for physical and mental QOL respectively. Multiple regression analysis revealed that age, employment status (employed), marital status (unmarried/divorced/widowed) and high needs in physical symptoms were associated with physical QOL. In addition, gender (female), marital status (unmarried/divorced/widowed), and needs in health and psychological problem and physical symptoms domains are significant factors to the mental QOL. These findings from the study provide useful information for care providers to identify and meet specific needs for cancer patients to improve QOL.

Analysis of serum microRNA expression in male workers with occupational noise-induced hearing loss.

Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3) and ONIHL subjects (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3' UTR segment of MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05). This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.

[Screening and cloning of genes encoding Schistosoma japonicum antigens related to the serum antibodies in Mirotus fortis].

OBJECTIVE: To understand and identify the molecules related to the natural resistance to Schistosoma japonicum infection in Mirotus fortis. METHODS: Sera from Mirotus fortis without schistosome infection were collected. The S. japonicum adult worm cDNA library was immunologically screened with the sera. The positive recombinants were identified, cloned, sequenced and analysed with software and internet. RESULTS: Seven genes encoding antigens relevant to sera antibodies in Mirotus fortis were cloned and sequenced. These antigens included glyceraldehyde 3-phosphate dehydrogenase (GAPDH), serine protease inhibitors (SERPIN), 70 kDa heat shock protein (HSP70), 22.6 kDa membrane-associated antigen, paramyosin (Sj97), cytochrome C and cathepsin B. CONCLUSION: Many protein molecules might have been involved in natural resistance to S. japonicum infection in Mirotus fortis. The above 7 kinds of molecules may be identified as new candidates of vaccine against S. japonicum infection.

A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein.

Despite their significance for mammalian embryogenesis, the molecular mechanisms that regulate placental growth and development have not been well defined. The Esx1 homeobox gene is of particular interest because it is among the few regulatory genes that have specific expression and function in the placenta during murine development. In addition, the ESX1 protein contains several notable features that are not often associated with homeoproteins, including an atypical homeodomain of the paired-like class, a proline-rich region that contains an SH3 binding motif, and a novel repeat region consisting of prolines alternating with phenylalanines or asparagines that we term the PF/PN motif. We have found that the ESX1 protein is expressed in the labyrinth layer of the placenta in vivo, where its subcellular localization is primarily cytoplasmic. Our results suggest that this unexpected subcellular localization is conferred by the PF/PN motif, which inhibits nuclear localization of ESX1 in cell culture, as well as its DNA binding activity in vitro. Finally, we show that the proline-rich region of ESX1 mediates interactions in vitro with the c-abl SH3 domain as well as with certain WW domains. We propose that the PF/PN motif provides a novel mechanism for regulating nuclear entry and that the essential function of ESX1 during placental development is mediated by its ability to couple cytoplasmic signal transduction events with transcriptional regulation in the nucleus.

Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation.

Specification of the left-right (L-R) axis in the vertebrate embryo requires transfer of positional information from the node to the periphery, resulting in asymmetric gene expression in the lateral plate mesoderm. We show that this activation of L-R lateral asymmetry requires the evolutionarily conserved activity of members of the EGF-CFC family of extracellular factors. Targeted disruption of murine Cryptic results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and pulmonary right isomerism, as well as randomized embryo turning and cardiac looping. Similarly, zebrafish one-eyed pinhead (oep) mutants that have been rescued partially by mRNA injection display heterotaxia, including randomization of heart looping and pancreas location. In both Cryptic and oep mutant embryos, L-R asymmetric expression of Nodal/cyclops, Lefty2/antivin, and Pitx2 does not occur in the lateral plate mesoderm, while in Cryptic mutants Lefty1 expression is absent from the prospective floor plate. Notably, L-R asymmetric expression of Nodal at the lateral edges of the node is still observed in Cryptic mutants, indicating that L-R specification has occurred in the node but not the lateral plate. Combined with the previous finding that oep is required for nodal signaling in zebrafish, we propose that a signaling pathway mediated by Nodal and EGF-CFC activities is essential for transfer of L-R positional information from the node.

Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo.

The anterior-posterior axis of the mouse embryo is established by two distinct organizing centres in the anterior visceral endoderm and the distal primitive streak. These organizers induce and pattern the head and trunk respectively, and have been proposed to be localized through coordinate cell movements that rotate a pre-existing proximal-distal axis. Here we show that correct localization of both head- and trunk-organizing centres requires Cripto, a putative signalling molecule that is a member of the EGF-CFC gene family. Before gastrulation, Cripto is asymmetrically expressed in a proximal-distal gradient in the epiblast, and subsequently is expressed in the primitive streak and newly formed embryonic mesoderm. A Cripto null mutation generated by targeted gene disruption results in homozygous Cripto-/- embryos that mostly consist of anterior neuroectoderm and lack posterior structures, thus resembling a head without a trunk. Notably, markers of the head organizer are located at the distal end of the embryo, whereas markers of the primitive streak are absent or localized to the proximal side. Our results indicate that Cripto signalling is essential for the conversion of a proximal-distal asymmetry into an orthogonal anterior-posterior axis.

Antiaggregatory activity of 8-epi-prostaglandin F2 alpha and other F-series prostanoids and their binding to thromboxane A2/prostaglandin H2 receptors in human platelets.

8-Epi-prostaglandin F2 alpha (8-epi-PGF 2 alpha) is a nonenzymatic, free radical-catalyzed peroxidation product of arachidonic acid that has potent biological activity, including contraction of vasculature and inhibition of aggregation induced by thromboxane (TX) A2 mimetics. In the present study, we demonstrate that 8-epi-PGF2 alpha could inhibit platelet aggregation induced by the TX mimetics U46619 and I-BOP as well as low-dose collagen but not thrombin or the primary wave of aggregation caused by high-dose ADP. The secondary (TX-dependent) wave of aggregation induced by high-dose ADP, however, was not affected. This suppression was dose dependent where 3.6 and 3.3 microM of 8-epi-PGF2 alpha caused 50% inhibition of platelet aggregation induced by U46619 and I-BOP, respectively, whereas 10 microM caused approximately 72% inhibition of collagen-induced aggregation. In contrast, 8-epi-PGF2 alpha significantly potentiated reversible platelet aggregation in response to low-dose ADP. These results indicate that 8-epi-PGF2 alpha has partial agonist activity. 9 alpha,11 beta-PGF2, a structural isomer of 8-epi-PGF2 alpha, inhibited platelet aggregation induced by collagen, high- and low-dose ADP and thrombin, demonstrating marked differences between structural isomers where 9 alpha,11 beta-PGF2 inhibited platelet aggregation induced by TX-dependent as well as TX-independent stimuli. In addition to platelet aggregation, we performed competition-binding assays on washed human platelets using [125I]BOP to further investigate the interaction of 8-epi-PGF2 alpha and 9 alpha,11 beta-PGF2 with TXA2/PGH2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Different methods for wound management of radiation-burn injury in rats.

Different methods of burn wound management were used in rats with severe radiation-burn injury. The 30-day survival rate and the functional recovery of thymocytes and splenocytes were significantly higher in the group with early escharectomy and skin grafting than in the group without operational intervention and in the group with skin grafting in the recovery stage. In the group with early escharectomy and skin grafting on the 1st day after injury, all the autografts survived and the survival of the homografts was also markedly prolonged. Escharectomy and skin grafting performed in the late stage aggravated the wound condition, and infection and hemorrhage were the main factors hastening the death of the skin grafts as well as the animals. The findings indicate that escharectomy and skin grafting in the early stage after injury are conducive to the recovery of immune function and consequently to the recovery of the whole organism because infections are minimized after escharectomy and closure of the wound surfaces by skin grafting.

[Effect of burn injury, blast injury and combined burn-blast injury on immune reactions of thymocytes and splenocytes in rats].

Rats were inflicted with burn (15% TBSA full-thickness) by flash thermal radiation, blast injury in shock tube (over pressure 429.3 +/- 11.5 kPa) and both of them, respectively. The dynamic changes of several cellular immune reactions of thymocytes and splenocytes were observed. One hour after injuries, the immune reactions were significantly enhanced in combined injury group as well as in blast injury group, but somewhat depressed in burn group. 12 hours after injuries, the immune reactions in all three groups were obviously depressed. It was found that the degree of depression showed an order as follows: Combined injury > Blast injury > Burn. The combined effects were more serious than that of the sum of two single injuries, and the combined injury recovered more slowly than the other two. Therefore, an aggravated effect was observed in combined injury in this experiment.

14(R),15(S)-epoxyeicosatrienoic acid (14(R),15(S)-EET) receptor in guinea pig mononuclear cell membranes.

A high affinity binding site for 14(R),15(S)-EET, one of the major cytochrome P-450 metabolites of arachidonic acid (AA) in blood vessels, liver, kidney and urine of patients with pregnancy-induced hypertension, has been identified in a membrane preparation from guinea pig mononuclear (GPM) cells. Using a radioligand assay, binding of 14(R),15(S)-[3H]EET to its receptor site was saturable, specific and reversible. Scatchard analysis of saturation binding studies yielded a dissociation constant (Kd) of 5.7 x 10(-9) M, and maximum number of binding sites (Bmax) of 2.4 pmol/mg membrane protein. The specificity of the binding site was determined by competition studies. 14(S),15(R)-EET and 8,9-EET had a Ki of 6.3 and 8.8 nM, respectively, followed by 12(R)-HETE and LTD4. 12(S)-HETE and 5,6-EET were even less effective as a competitive inhibitor of radioligand and binding with Ki values from 2 to 20 microM. Receptor antagonists for TxA2, LTB4, LTD4 and PAF failed to displace 14(R),15(S)-[3H]EET from its binding site on GPM cell membranes. The results correlate well with the reported biological functions of 14,15-EET. In view of its potent biological activities, 14,15-EET may exert its cellular function through the binding and activation of its stereo-specific cell surface binding sites or receptor.