Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.

Objective To demonstrate high mobility group box chromosomal protein 1(HMGBI) expression in synovium and joint,and to identify the role of HMGB1 in the pathogenesis of synovitis and joint destruction in adjuvant-induced arthritis(AA).Methods AA of 15 male rats were induced in SD rats by intradermal injection of 100?l Freud's complete adjuvant in the foot pad of the left hind paw.All rats were killed at the 18th day.Synovium and joints were collected for histopathology studies and determining the expression of HMGB1 by immunohistochemistry,and serum was collected for determining the expression of HMGB1 by western blotting analysis.Results Immunostaining of specimens from normal rats showed that HMGB1 was primarily confined to the nucleus of synoviocytes with occasional cytoplasmic staining.In contrast, inflammatory synovial tissues from AA rats showed a distinctly different HMGB1 staining pattern.Nuclear HMGBI expression was accompanied by a cytoplasmic staining in many mononuclear cells.The cytoplasmic HMGB1 expression in synovium of AA rats is significantly higher than that of normal rats.Additionally,HMGBI was highly expressed in the nuclei and cytoplasm of the subchondral chondrocytes and inflammatory cells in bone erosion in AA rats(P＜0.01),while fewer positive cytoplasmic staining of HMGB1 was found in chondrocytes and fewer positive nuclear staining was found in bone cells in normal rats.HMGB1 concentration was significantly higher in serum of AA rats than that in normal rats(P＜0.001).Conclusion The cytoplasmic HMGBI expression in synovium and joints is greatly upregulated;the level of HMGB1 in serum is increased in AA rats which suggests a patbogenetic role of HMGB1 in synovitis and bone destruction of adjuvant-induced arthritis.

Adolescent ; Adult ; Dust ; Female ; Humans ; Male ; Mental Health ; statistics & numerical data ; Middle Aged ; Occupational Exposure ; Steel ; Surveys and Questionnaires

Acute pancreatitis (AP) is a common clinical emergency. Aseptic inflammation caused by the death of acinar cells is the early pathological change of AP. However, the main mechanism of aggravation of AP is the subsequently excessive inflammation which leads to multiple organ dysfunctions. Among them, the assembly and activation of inflammatory corpuscles are involved in the pathogenesis. It has shown that metabolic regulation of inflammatory corpuscle activation and its regulatory effectors play an important and decisive role in AP and its inflammatory response mechanism. This article reviews the structure and function of inflammasomes and their role in the pathogenesis of AP.

OBJECTIVETo observe the effect of Guilingji Capsule (GC) on the fertility, liver functions, and serum lactate dehydrogenase (LDH) of adult male SD rats exposed by 900 MHz cell phone.

METHODSTotally 18 adult male SD rats and 36 adult female rats in child-bearing period were selected and randomly divided into three groups according to weight equilibrium principle, i.e., the normal group, the radiated group, and the GC group, 6 males and 12 females in each group. Male rats in the normal group and all female rats were not radiated. Male rats in the radiated group and the GC group received radiation for 4 h per day, lasting for 18 successive days. Rats in the GC group received GC suspension at the daily dose of 0. 15 g/kg by gastrogavage at the same time. Equal volume of normal saline was administrated to other male rats. Then male rats were mated with corresponding female rats from the 14th radiation night to the 18th radiation night in the ratio of 1:2. Male rats were killed following on the next morning of ending the radiation. Female rats were normally fed and then killed before delivery. The pregnant outcomes of female rats in responding groups (the rates of pregnancy and the number of death fetus, birth weight, body length, and tail length) were observed and compared. Serum alanine aminotransferase (ALT), aspartate transferase (AST), AST/ALT, and LDH levels of the male rats were detected by colorimetry. Histological and morphological changes of liver were observed by HE staining.

RESULTSCompared with the normal group, the pregnancy rates of female rats decreased and the number of death fetus increased, the serum LDH level obviously increased in the radiated group (P < 0.05). Serum levels of ALT, AST, and AST/ALT were no significantly changed in the radiated group. The hepatocyte nuclear atrophy and cytoplasm vacuolar degeneration appeared. Compared with the radiated group, the pregnancy rates increased, the number of death fetus dropped, and the serum level of LDH decreased in the GC group (P < 0.05). There was no obvious change in serum levels of ALT, AST, or AST/ALT. The hepatocyte nuclear atrophy and cytoplasm vacuolar degeneration were significantly attenuated. The histomorphological structures recovered to normal basically in the GC group.

CONCLUSIONSThe pregnancy rates could be decreased, the number of death fetus increased, histomorphological structures abnormal, and serum LDH level increased by exposure toy GSM 900 MHz cell phone. GC could prevent and treat the aforesaid lesion. But there was no statistical difference in serum ALT or AST levels.

Animals ; Cell Phone ; Drugs, Chinese Herbal ; pharmacology ; Female ; Fertility ; Lactate Dehydrogenases ; blood ; Liver ; drug effects ; Male ; Pregnancy ; Radiation ; Rats ; Rats, Sprague-Dawley

Objective To find out severity and types of syphilis infection in blood donors, attendants and persons to have their premrital medical examination in Zhoushan City and offer a new measure for prevention and treatment of syphilis. Methods Totally, 174 589 blood donors, attendants and persons to have their premarital medical examinations were screened preliminarily for inapparent syphilis with non-TPHA, and then TPHA was applied to confirm the diagnosis, according to the National Standard No. GB 15974-1995, combining with clinical symptoms and physical check-up. Results A total of 1 327 cases of syphilis from 174 589 samples tested, including blood donors, attendants and persons to have their premarital medical examinations, were diagnosed, with an inapparent infection rate of 7. 60‰ in average, 6. 42‰in males and 8. 74‰ in females, with a sex ratio of 0.71 (X2 = 29. 92, P

AIM:To investigate the expression and significance of thrombospondin-1(TSP-1)in left ventricular myocardium of type 2 diabetic cardiomyopathy(DCM).METHODS:The rat model of DCM was established by eating a high-fat diet together with injection of low dose streptozocin(30 mg/kg)intrapertoneally.After 12 weeks,the content of collagen was quantified by Masson staining.The mRNA level of TSP-1 was determined by quantification real-time RT-PCR,while the protein level of TSP-1 was analyzed by Western blotting and immunohistochemistry.RESULTS:Compared with the control group,the content of collagen in the DCM group was increased greatly(11.01?3.05 vs 16.92?3.18,P

Objective: To analyze the effect of acupuncture versus hormone replacement therapy (HRT) for premature ovarian insufficiency (POI). Methods: China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), Web of Science, Cochrane Library, PubMed, and Excerpta Medica Database (EMBASE) were searched up to January 31st, 2019 to identify randomized controlled trials (RCTs) evaluating the effect of acupuncture for POI. The primary outcome was the level of basal serum follicle- stimulating hormone (FSH). Secondary outcomes included serum levels of luteinizing hormone (LH), estradiol (E2) and anti-Müllerian hormone (AMH). Two authors extracted data independently and assessed the risk of bias and the methodological quality using the Cochrane's tool. Meta-analysis was conducted by RevMan version 5.3. Results: Eight eligible RCTs with a total of 496 POI patients were included in the meta-analysis. The pooled results showed that there was a significant reduction in the basal serum FSH level (MD=-5.82, 95％CI:-9.76 to -1.87, I2=82％, P=0.004) and a remarkable elevation in the basal E2 level (SMD=0.93, 95％CI: 0.34 to 1.52, I2=88％, P=0.002) in the acupuncture group when compared with the control. Subgroup analysis showed that compared with HRT, a significant decrease in the FSH level was observed in both acupuncture alone (MD=-4.53, 95％CI:-8.96 to -0.10, I2=73％, P=0.04) and acupuncture plus HRT (MD=-9.60, 95％CI:-17.60 to -1.61, I2=50％, P=0.02), while a remarkable elevation of E2 was only found in acupuncture plus HRT (SMD=1.43, 95％CI: 1.03 to 1.82, I2=0％, P<0.00001). There was no significant difference in the LH level between acupuncture and HRT (MD=-3.16, 95％CI:-9.41 to 3.10, I2=0％, P=0.32), only one trial reported AMH, and no significant difference was found between acupuncture and HRT. Conclusion: The present study indicated that acupuncture had an advantage over HRT in reducing serum FSH level and increasing serum E2 level in women with POI. However, evidence supporting the finding is limited due to the small sample size, potential methodological flaws and significant heterogeneity. Hence, this conclusion still needs to be verified by high-quality RCTs.

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

OBJECTIVETo search for chemical constituents with structural diversity from Laurencia tristicha to supply for biological assay.

METHODCompounds were isolated by means of column chromatography over normal phase silica gel and Sephadex LH-20, recrystallization and HPLC. Structures were identified by spectroscopic methods including 1D NMR, IR and MS. Cytotoxicities of the purified compounds were evaluated by MTT method.

RESULTSeven compounds were isolated from L. tristicha. Their structures were elucidated as cholesterol (1), cholesta- 5-en-3beta, 7alpha-diol (2), beta-stigmasterol (3), phytol (4), zeaxanthin (5), 4 -hydroxybenzaldehyde (6), indolyl-3-carbaldehyde (7). In the cytotoxic assay compound 2 was active against human cancer cell lines HCT-8, Bel-7402, BGc-823, A549 and HELA with IC50 values of 1.90, 2.02, 1.99, 6.52 and 1.20 microg x mL(-1), respectively. Compound 4 showed cytotoxicity against HCT-8 and HELA with IC50 value of 3.51 and 2.04 microg x mL(-1), and other compounds were inactive ( IC50 > 10 microg x mL(-1)).

CONCLUSIONCompounds 1-7 were isolated from L. tristicha for the first time. In additon, compounds 2 and 4 were cytotoxic against several human cancer cell lines.

Antineoplastic Agents ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; drug effects ; Cholestenes ; chemistry ; isolation & purification ; pharmacology ; Cholesterol ; chemistry ; isolation & purification ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Laurencia ; chemistry ; Phytol ; chemistry ; isolation & purification ; pharmacology