CARD9S12N facilitates the production of IL-5 by alveolar macrophages for the induction of type 2 immune responses.

The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH1 and TH17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs. Mechanistically, CARD9S12N mediated CLR-induced activation of the non-canonical transcription factor NF-κB subunit RelB, which initiated production of the cytokine IL-5 in alveolar macrophages for the recruitment of eosinophils to drive TH2 cell-mediated allergic responses. We identified the homozygous CARD9 mutation encoding S12N in patients with allergic bronchopulmonary aspergillosis and revealed activation of RelB and production of IL-5 in peripheral blood mononuclear cells from these patients. Our study provides genetic and functional evidence demonstrating that CARD9S12N can turn alveolar macrophages into IL-5-producing cells and facilitates TH2 cell-mediated pathologic responses.

[Role of Bone Marrow Cell Morphology Combined with Immunohistochemistry Examinations in the Diagnosis of Patients with Primary Bone Marrow Lymphoma].

OBJECTIVE: To explore the diagnostic value of bone marrow cell morphology combined with immunohistochemistry in patients with primary bone marrow lymphoma. METHODS: The clinical data of 23 patients with primary bone marrow lymphoma diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 were collected. The characteristics of bone marrow aspiration, bone marrow biopsy and immunohistochemistry results were analyzed retrospectively, and the diagnostic value of bone marrow cell morphology combined with immunohistochemistry in primary bone marrow lymphoma were clarified. RESULTS: Most of primary bone marrow lymphoma was B-cell lymphoma, among which diffuse large B-cell lymphoma was the most common pathological type. Typical lymphoma cells could be found in all the patients. 78.26% of the patients could be diagnosed as lymphoma with pathological type, while 91.30% were diagnosed as lymphoma through combined with the bone marrow immunohistochemistry. CONCLUSION: Bone marrow cell morphology combined with immunohistochemistry shows very important diagnostic value in patients with primary bone marrow lymphoma.

[An experimental study on pulmonary toxicity water extracts of Siegesbeckia pubescens on mice].

OBJECTIVE: The pulmonary toxicity of water extract of Siegesbeckia pubescens has been studied an mice following subchronic oral administration route. METHOD: Mice were randomly grouped and administered with the water extract of S. pubescens at dosages of 3.0, 1.0, 0.3 g x kg(-1) and saline respectively. 10 mice of each group were sacrificed on the day of 7 th, 14 th, 21 th, and 2 weeks after stopping administration, histological changes of the lung were examined. RESULT: The water extract of S. pubescens at dosage of 3.0 g x kg(-1) increased the lung index on the of day 14 th and 21 th, significant histopathological damages were observed. The histopathological changes were disappeared after stopping administration for 2 weeks. CONCLUSION: The water extract of S. pubescens has a pulmonary toxic effect on mice, and the toxic effect is reversible.

[Pathological Characteristics of Bone Marrow in Multiple Myeloma Patients with Secondary Myelofibrosis and Their Relationship with Prognosis].

OBJECTIVE: To investigate the pathological characteristics of bone marrow in multiple myeloma patients with secondary myelofibrosis and their relationship with prognosis. METHODS: Clinical data of 70 cases of multiple myeloma including 35 patients with secondary myelofibrosis were analyzed retrospectively from January 1st to December 31st 2012 in Department of Hematology of our hospital, the degree of hyperplasia, as well as the changes of myelofibros after treatment were compared between bone marrow smear and biopsy, and their relationship with the prognosis was analysed. RESULTS: The myelofibrosis could be observed in any stage and type of multiple myeloma, the myelobibrosis could cause the decrease of pseudoepitheliomatous hyperplasia in bone marrow smear, and the increase of reticulin could be observed in the biopsy with Gomori staining + to +++, and the secondary myelofibrosis could be alleviated after treatment. The overall prognosis of these patients was poor. CONCLUSION: The bone marrow biopsy has the important diagnostic value for the multiple myeloma patients with secondary myelofibrosis, and the myelofibrosis can be alleviated after treatment, but the overall prognosis of multiple myeloma patients with secondary myelofibrosis is poor.

[Significance of Simultaneous Analysis of Bone Marrow Smear and Bone Marrow Biopsy in the Diagnosis of Lymphoma].

OBJECTIVE: To explore the value of bone marrow smear combined with biopsy in the diagnosis of lymphoma. METHODS: Clinical data of 50 cases of lymphoma from our hospital were analyzed retrospectively, and the results of the bone marrow smear and the bone marrow biopsy were compared simultaneously. RESULTS: The decision for the degree of bone marrow hyperplasia in bone marrow biopsy slice was superior to that in smear, and the active or highly active hyperplasia of nucleated cells were observed in all the bone marrow biopsies; the lymphomatic cells were observed in bone marrow smear of the 12 patients(24%), but the bone marrow biopsies showed a higher detection rate of lymphomatic cells 44% in 22 patients(P<0.05); The hyperplasia of bone marrow fibrous tissue, mainly mild to moderate, were the common in cases with bone marrow involvement and the severity of bone marrow fibrosis positively correlated with the number of lymphomatic cells. CONCLUSION: Biopsy combined with aspiration can improve the accuracy of diagnosis in lymphoma with bone marrow involvement.

[Influence of the watery extract of jiangzhining decoction on the genetic expression of hepatocyte LDLR of hyperlipidemic rats].

OBJECTIVE: To study the influence of Jiangzhining decoction on the genetic expression of Liver LDLR of the rats suffered from hyperlipemia. METHOD: Laboratory animals were male wister rats with hyperlipemia resulting from high fat feeding. Prescription was the douche of stomach with Jiangzhining decoction (200%) with a dosage of 1.4 g.kg-1, for 15 successive days. Total RNA was extracted from the liver tissue of treated rats and LDLRmRNA was detected by Dot blot hybridization. Expression levels of LDLRmRNA was estimated by a ratio of LDLRmRNA and beta-actin mRNA. RESULT: The difference between expression levels of LDLRmRNA for normal group and those for hyperlipemia group (100% +/- 19% vs 39% +/- 14%) was significant (P < 0.05); and the difference between decoction group (108 +/- 8%) and hyperlipimia group was also highly significant (P < 0.01). CONCLUSION: High fat feeding reduces the expression of liver LDLRmRNA while the decoction can greatly increase it. The study and development of Jiangzhining are significant in preventing and curing cadiocerebral diseases.

CARD9 mediates Dectin-1-induced ERK activation by linking Ras-GRF1 to H-Ras for antifungal immunity.

Dectin-1 functions as a pattern recognition receptor for sensing fungal infection. It has been well-established that Dectin-1 induces innate immune responses through caspase recruitment domain-containing protein 9 (CARD9)-mediated NF-κB activation. In this study, we find that CARD9 is dispensable for NF-κB activation induced by Dectin-1 ligands, such as curdlan or Candida albicans yeast. In contrast, we find that CARD9 regulates H-Ras activation by linking Ras-GRF1 to H-Ras, which mediates Dectin-1-induced extracellular signal-regulated protein kinase (ERK) activation and proinflammatory responses when stimulated by their ligands. Mechanistically, Dectin-1 engagement initiates spleen tyrosine kinase (Syk)-dependent Ras-GRF1 phosphorylation, and the phosphorylated Ras-GRF1 recruits and activates H-Ras through forming a complex with CARD9, which leads to activation of ERK downstream. Finally, we show that inhibiting ERK activation significantly accelerates the death of C. albicans-infected mice, and this inhibitory effect is dependent on CARD9. Together, our studies reveal a molecular mechanism by which Dectin-1 induces H-Ras activation that leads to ERK activation for host innate immune responses against fungal infection.

[Pathological characteristics of leukemia patients with secondary myelofibrosis and their relationship with the prognosis of disease].

The objective of this study was to investigate the pathological characteristics of leukemia patients with secondary myelofibrosis and their relationship with prognosis. The pathological characteristics of 29 leukemia patients with secondary myelofibrosis were observed, the degree of hyperplasia between bone marrow smear and biopsy, as well as the changes of myelofibrosis after treatment were compared, and their relationship with the prognosis was analysed. The results indicated that the myelofibrosis may cause the decrease of pseudoepitheliomatous in bone marrow smear, and the increase of reticulin could be observed except the primary pathological characteristics in the biopsy with Gomori staining ++ - +++, and the secondary myelofibrosis could be alleviated after treatment. The overall prognosis of these patients was poor. It is concluded that the bone marrow biopsy has the important diagnostic value for the leukemia patients with secondary myelofibrosis, and the myelofibrosis can be alleviated after treatment, but the overall prognosis of leukemia patients with secondary myelofibrosis is poor.

[One-step method of bone marrow aspiration and biopsy applied in diagnosis of the bone marrow metastatic cancer].

This study was aimed to explore the value of one-step method of bone marrow aspiration and biopsy applied in diagnosis of the bone marrow metastatic cancer. The total of 46 cases of bone marrow metastatic cancer were analyzed retrospectively, and the results of the bone marrow smear and the bone marrow biopsies were compared. The results indicated that the success rate of one-step method of bone marrow aspiration and biopsy was 95.7%. Metastatic carcinoma cells in clumps or clusters with morphological changes were observed in the bone marrow biopsies of the 45 patients (97.8%), but the metastatic carcinoma cell clusters were observed only in bone marrow smears of the 25 patients (54.3%). There were mild to moderate hyperplasia of fibrous tissue in the patients with metastatic cancer. In addition to the 83.3% diagnostic rate of esophageal cancer, the rest diagnostic rate of bone marrow biopsy for metastatic carcinoma was 100%. The diagnostic rate of bone marrow smear for ovarian cancer, lung cancer, gastric cancer, thoracic tumor, sigmoid colon cancer, esophageal cancer and metastatic cancer of unknown primary cancers were 33.3%, 50%, 72.2%, 60%, 50%, 33.3% and 25%, respectively. The diagnostic rate of bone marrow biopsy was higher than that of bone marrow smear. It is concluded that the success rate of drawing specimen by one-step method of bone marrow aspiration and biopsy is high. The bone marrow biopsy is better than that of aspiration in diagnosis of metastatic cancer. Combining biopsy with aspiration can improve the accuracy of diagnosis.