Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.

This study was purposed to investigate the ratio of Th17 cells and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood of patients with chronic lymphocytic leukemia (CLL) and to explore their roles in the pathogenesis and clinical diagnosis. Based on the number of peripheral lymphocytes and treatment condition, the CLL patients were divided into 2 groups: untreated group (n = 30) and remission group (n = 15), the healthy control group (n = 20) was set up as well. The frequencies of Th17 and Treg cells of all cases were detected by flow cytometry (FCM). The results showed that frequencies of CD3(+)CD4(+)T cells and Th17 cells were significantly higher in untreated group than that in healthy control group (P < 0.05), the frequencies of CD3(+)CD8(+)T cells and Treg cells were significantly lower in untreated group than that in healthy control group (P < 0.05), the ratio of Th17/Treg was significantly higher in untreated group than that in healthy control group (P < 0.05). The frequencies of Th17 were not statistically different between remission and healthy control groups, the frequencies of Treg cells were significantly lower in remission group than that in healthy control group (P < 0.05), the ratio of Th17/Treg was significantly higher in remission group than that in healthy control group (P < 0.05), frequencies of Th17 cells were markedly lower in remission group than that in untreated group (P < 0.05). It is concluded that Th17/Treg imbalance exists in patients with CLL, which may play a key role in pathogenesis and development of CLL.
Aged ; Case-Control Studies ; Female ; Flow Cytometry ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; pathology ; Lymphocyte Count ; Male ; Middle Aged ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology

Colorectal Neoplasms ; complications ; Humans ; Male ; Middle Aged ; Neck ; pathology ; Rectal Neoplasms ; complications ; Skin Neoplasms ; diagnosis ; pathology ; secondary ; Thorax ; pathology

AIM:To investigate the mutation of FLT3-ITD gene in the patients with newly diagnosed acute myeloid leukemia (AML). METHODS:From March 1, 2015 to June 1, 2017, 207 patients with AML admitted to de-partment of hematology, sichuan provincial people′s hospital were enrolled in this study. The bone marrow samples were collected from the patients. PCR was used to detect the mutation of FLT3-ITD gene. After the corresponding chromosome was obtained by R-banding, the cells were made into strips and banding. Twenty karyotypes with relatively cleavage were automatically selected from each specimen to complete karyotyping. By analysis of the clinical data and following-up the prognosis, the FLT3-ITD gene mutation in diagnostic and evaluative values for AML were performed. RESULTS:FLT3-ITD gene mutation was found in 42 cases of 207 AML patients, the positive rate was 20. 29 % . FLT3-ITD positive patients showed 3 bands. FLT3-ITD gene mutation in 42 patients with positive results showed that FLT3-ITD gene mutations in turn met the end to end, and insert a number of nucleotides, but all the mutations were in-frame mutations. According to the FAB and WHO standard, in 42 cases of FLT3-ITD positive positive patients, M0 accounted for 0.00% , M1 accounted for 2.38% (1/42), M2 accounted for 23.81% (10/42), M3 accounted for 0.00% , M4 accounted for 2.38% (1/42), M5 accounted for 69.05% (29/42), M6 accounted for 0.00% , M7 accounted for 2.38% (1/42). The white blood cell ( WBC) level and complete response (CR) rate in FLT3-ITD positive patients were lower than those in FLT3-ITD negative patients (P<0.05). CONCLUSION:The WBC level and CR rate, which are lower in FLT3-ITD positive patients than those in negative patients, are the clinical risk factors. It will be helpful to determine the prognosis evaluation for AML pa-tients.

OBJECTIVETo investigate the ratio of Th17 cells and CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells in peripheral blood from patients with multiple myeloma (MM) and explore its pathological effects.

METHODS70 MM patients were divided into three groups: newly diagnosed group (n=30), plateau stage group (n=23) and relapsed/refractory group (n=17). The controls consisted of 20 healthy donors. The frequencies of Th17 and Treg cells were detected by flow cytometry.

RESULTSCompared with controls [(0.72±0.33)%] and plateau stage group [(0.74±0.29)%], frequencies of Th17 cells were higher in newly diagnosed group [(1.62±0.65)%] and relapsed/refractory group [(1.45±0.51)%], respectively (P<0.05). Compared with controls [(2.33±0.90)%] and plateau stage group [(1.69±0.70)%], frequencies of Treg cells were significantly lower in newly diagnosed group [(0.55±0.23)%] and relapsed/refractory group [(0.82±0.54)%], respectively (P<0.05). The ratios of Th17/Treg in newly diagnosed group and relapsed/refractory group were higher than those in controls (P<0.05). There were no differences of the frequencies of CD3⁺CD4⁺ T cells and Th17 cells between plateau stage group and controls. The frequencies of Treg cells were significantly lower in plateau stage group than that in controls (P<0.05), and the ratio of Th17/Treg was significantly higher in plateau stage group than that in controls (P<0.05).

CONCLUSIONThe remarkable abnormality of T cells subsets was reduction of CD4⁺ T cells in MM. Higher frequency of Th17 and lower ratio of Treg could lead to imbalance of Th17/Treg, which may play a critical role in the pathogenesis of MM.

Adult ; Aged ; Female ; Flow Cytometry ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Multiple Myeloma ; immunology ; pathology ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology

OBJECTIVETo establish a method for organotypic slice culture of neonatal rat cortex in a modified condition and investigate the effect of spatial signals on neural stem cell (NSC) differentiation.

METHODSThe brain slices (200 µm in thickness) of neonatal SD rats (3 to 5 days old) were prepared and cultured in modified serum-free DMEM/F12 medium at 37 degrees celsius; with 95% O(2) and 5% CO(2). The organotypic slice cultures were observed regularly. NSCs isolated from the cortex of rat embryos (14-15 embryonic days) were cultured in serum-free DMEM/F12 supplemented with B27 and N2, and the passage 3 NSCs were labeled by CM-DiI before transplanted onto the organotypic slices cultured for 2 weeks. The survival of transplanted NSCs was assessed, and the cell differentiation was identified by immunofluorescence staining.

RESULTSThe organotypic slice cultures were well maintained for at least 4 weeks in the modified medium. The thickness of the organotypic slices reduced from 200 µm to 130 µm after 2-week culture in vitro due to the migration of the cells on the edge of the slices. CM-DiI-labeled NSCs survived well and differentiated into GFAP(+) glia and β-tubullin III(+) neurons.

CONCLUSIONNeonatal rat organotypic brain slice can be successfully cultured in a modified condition to serve as a model for studying NSC differentiation induced by spatial signals.

Animals ; Animals, Newborn ; Cell Differentiation ; physiology ; Cerebral Cortex ; cytology ; Coculture Techniques ; methods ; Fetus ; Neural Stem Cells ; cytology ; transplantation ; Organ Culture Techniques ; methods ; Rats

OBJECTIVETo explore the effects of salidroside (sal) on the expressions of Bcl-2, Bax and caspases-3 proteins in cultured rat subventricular zone (SVZ) neural stem cells (NSCs) exposed to hypoxia injury.

METHODSPrimarily cultured SVZ NSCs from adult SD rats were incubated with salidroside (120 and 240 µmol/L) for 24 h prior to exposure to hypoxia. The cell viability was assessed with MTT assay, and the cell apoptosis was analyzed using TUNEL staining and flow cytometry. Western blotting was performed to detect the expressions of Bcl-2, Bax and caspase-3 in the cells.

RESULTSSalidroside pretreatment of the cells for 24 h resulted in an obvious resistance to hypoxia-induced cell apoptosis and decrement of cell viability (P<0.05). Salidroside also antagonized the effect of hypoxia exposure in lowering Bcl-2/Bax ratio apoptosis of rat neural stem cells and decreased the expression of caspases-3 protein (P<0.05).

CONCLUSIONSalidroside can significantly resist hypoxia-induced. The neuroprotective effect of salidroside may be related to the modulation of expressions of apoptosis-related proteins.

Animals ; Caspase 3 ; metabolism ; Cell Hypoxia ; Cells, Cultured ; Flow Cytometry ; Glucosides ; pharmacology ; Neural Stem Cells ; drug effects ; Phenols ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) all over the world, there is an increasing number of children with such infection. Angiotensin-converting enzyme 2 (ACE2), one of the binding sites for SARS-CoV-2 infection in humans, can bind to viral spike proteins, allowing transmembrane serine protease (TMPRSS2) to activate S-protein to trigger infection and induce the production of various inflammatory factors such as interleukin-1, interferon-l, and tumor necrosis factor. Compared with adults, children tend to have lower expression levels of ACE2 and TMPRSS2, which are presumed to be associated with milder symptoms and fewer cases in children. The article summarizes the research advances in the role of ACE2 during SARS-CoV-2 infection, in order to help understand the pathogenic mechanism of SARS-CoV-2 and provide a reference for better development of drugs and vaccines to prevent and treat coronavirus disease 2019 in children.
Angiotensin-Converting Enzyme 2/metabolism* ; COVID-19 ; Child ; Humans ; Receptors, Virus/metabolism* ; SARS-CoV-2 ; Serine Endopeptidases/metabolism*

Objective:To compare the different follow-up methods on compliance and prognosis of non-selective beta blockers (NSBBs) for out-patients with secondary prevention of esophagogastric variceal bleeding (EGVB).Methods:A total of 72 patients with portal hypertension and esophageal gastric varices (EGV), who were admitted to the department of gastroenterology, Renmin Hospital of Wuhan University from July 2018 to April 2019 were randomly included in the traditional outpatient follow-up group (group A, 24), remote platform follow-up group (group B, 23) and combined follow-up group (group C, 25) according to the random number table. The patient′s medication compliance, heart rate response, condition change and treatment were recorded. NSBBs medication compliance, influencing factors and prognosis of patients in different groups were analyzed.Results:Forty (40/72, 55.6%) patients had good compliance with NSBBs, among which 34 (34/40, 85.0%) achieved heart rate response. The medication compliance of the group B (15/23, 65.2%) and the group C (17/25, 68.0%) was higher than that of the group A (8/24, 33.3%; χ2=4.778, P=0.029; χ2=5.889, P=0.015, respectively). There was no significant difference in the medication compliance between the group B and the group C ( χ2=0.042, P=0.838). In the group A, the subgroup of good compliance had higher proportion of local patients than that of poor compliance subgroup [7/8 VS 37.5% (6/16), P=0.033]. Patients with good drug compliance had higher proportion of gastroscopy review than that of poor compliance patients [75.0% (30/40) VS 21.9% (7/32), χ2=20.085, P<0.001] and less patients with EGVB [5.0% (2/40) VS 21.9% (7/32), P=0.073]. Conclusion:Patients with portal hypertension and EGV have poor compliance with NSBBs. Remote platform follow-up is a better way to improve compliance of drug prevention. Patients with good NSBBs compliance have a higher compliance of gastroscopy review. The risk assessment of variceal bleeding and endoscopic sequential therapy based on the results of gastroscopy review are expected to reduce the risk of EGVB.

Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration. Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed. Results: The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy. Conclusion: CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.
Adenine/analogs & derivatives* ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy* ; Piperidines ; Proto-Oncogene Proteins c-bcl-2 ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use* ; Recoverin ; T-Lymphocytes