Analysis of effective components of Agaricus blazei Murill extract by LC-MS and network pharmacology analysis in treatment of chronic myeloid leukemia / 中国药理学通报

Aim To explore the potential targets and related signaling pathways of Agaricus blazei Murill (AbM ) extract in the treatment of chronic myeloid leukemia (CML) based on liquid chromatography mass spectrometry ( LC-MS ), network pharmacology, molecular docking, and were further verified by experiments in vitro. Methods The active components of AbM extract were retrieved from LC-MS, Swiss Target Prediction database was used to predict related targets, and CML disease target genes were obtained from Gen- eCards and DisGeNET databases. After screening the common targets of drug and CML, the protein-protein interaction network of the common targets was performed by STRING, and GO and KEGG enrichment a- nalysis were done by DAVID database. Cytoscape software was used to construct the network of target protein. Molecular docking was carried out by DockThor, and the Pymol software was used to make a visual picture. The inhibitory effect of AbM extract on leukemia cells K562 was determined by CCK-8 experiment, and the effect of AbM extract on the expression and phosphorylation level of related proteins was verified by Western blot. Results The prediction results showed that 126 active components of AbM extract, and 172 common targets were collected. KEGG pathway analysis results showed that PI3K/Akt/mTOR signaling pathway might play an important role in the treatment of CML disease. The IC

Study on the Mechanism of Multi-Drug Resistance of Agaricus Blazei Extract FA-2-b-β Mediated Wnt Signaling Pathway to Reverse Acute T Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines.@*METHODS@#Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy.@*RESULTS@#Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified.@*CONCLUSION@#Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.

The regulating effect of Collybistin on Neuropathic Pain / 中国药理学通报

Aim To investigate the role of collybistin in the regulation of pain transmission. Methods The distribution of collybistin in spinal cord was observed by immunohistochemical staining. The role of collybis¬tin in pain transmission was evaluated by behavioral experiments. The effect of collybistin on inhibitory synap¬tic transmission was studied by electrophysiological ex¬periments. Results Collybistin was distributed in spi¬nal cord neurons; ShRNA-collybistin induced pain sen-sitization of intact mice ( P < 0. 05 ) . Overexpression of collybistin in spinal cord significantly alleviated pain sensitization induced by peripheral nerve injury ( P <0. 05 ) . ShRNA-collybistin also significantly reduced the amplitudes and frequencies of miniature inhibitory postsynaptic currents (mlPSCs) in superficial neurons of spinal cord dorsal horn (P <0. 05) . Overexpression of collybistin in spinal cord could reverse the effects of peripheral nerve injury on mlPSCs (P <0. 05). Con¬clusions Collybistin is involved in pain sensitization induced by peripheral nerve injury in mice.

Expression of CD56 in Multiple Myeloma Cells and Its Relationship with Extramedullary Disease and Extramedullary Relapse / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CD56 in multiple myeloma (MM) cells and its relationship between extramedullary disease and extramedullary relapse.@*METHODS@#Clinical data of 99 patients with MM treated in our hospital from January 2015 to December 2019 was retrospectively analyzed. The patients were divided into positive group and negative group according to the expression of CD56. The relationship between CD56 and multiple myeloma extramedullary disease, extramedullary relapse was analyzed.@*RESULTS@#Among 99 newly diagnosed patients with MM, the positive rate of CD56 was 65%, and the incidence of extramedullary disease of patients in the CD56 positive group was lower than that in the CD56 negative group (17.19% vs 48.57%) (P<0.01). Meanwhile, the incidence of extramedullary relapse of patients in the CD56 positive group was lower than that in the CD56 negative group (1.56% vs 34.29%) (P<0.01).@*CONCLUSION@#CD56 is highly expressed in MM, and its low expression is associated with the occurrence of extramedullary disease and extramedullary relapse, which suggests that CD56 may be an important indicator for predicting the occurrence of extramedullary disease and extramedullary relapse.

Primary Study on Chronic Myeloid Leukemia in NCG Mice from Qinba Mushroom / 中国实验血液学杂志

OBJECTIVE@#The present study was to evaluate the anti-tumor effects of acidic RNA protein complex (FA-2-b-β) extracted from the wild edible Qinba mushroom in inducing of apoptosis and immunoregulation of tumor cell.@*METHODS@#Cell proliferation inducing rate of FA-2-b-β to K562 cell was measured using CCK-8. Apoptosis rate was detected by using flow cytometry. Chronic myeloid leukemia model was developed by tail vein injection/subcutaneous inoculation of K562 cells in NCG mice. The tumor burden of mice was observed. The general condition of the mice was monitored twice daily. The peripherivcal full blood counts of mice was tested daily. RT-qPCR and Western blot was FA-2-b-β performed to determine involvement of apoptotic-related gene and protenin, Immunofluorescence and immunohistochemistry was used to detected the expression of CD3, CD4 and CD8.@*RESULTS@#The proliferation and apoptosis of K562 cell could be inhibitied and induced by FA-2-b-β, there was 100% successful in the tumor formation in vivo, after treated by drug for 21 days there were significantly increased peripheral leucocytes, but decreased hemoglobin of mice treated by FA-2-b-β as compared with those in control group. The CD3, CD4 and CD8 showed positive in mice, and the propotation was imbalance, but it showed reserved after treated by FA-2-b-β.@*CONCLUSION@#FA-2-b-β is strong anti-leukemia effect in vitro and in vivo, suggesting the traditional Chinese medicine maybe contribute to the anti-cancer and immunoregulation research.

Analysis on Related Factors of Pulmonary Infection in Patients with Multiple Myeloma Treated with Bortezomib / 中国实验血液学杂志

OBJECTIVE@#To analyze the risk factors, distribution of pathogenic strains and tolerance of pulmonary infection in patients with multiple myeloma(MM) during bortezomib chemotherapy.@*METHODS@#The clinical data of 85 patients with multiple myeloma treated by bortezomib in our hospital from January 2015 to January 2019 was analyzed. The patients were divided into infection group and control group according to whether they were infected. The tolerance, pathogen distribution, and related risk factors were retrospectively analyzed.@*RESULTS@#Pulmonary infection rate was 55.29% in 85 MM patients. The proportions of the patients with anemia, neutropenia, and ECOG score ≥2 points in the infection group were significantly higher than those in the control group (P<0.05). In this study, 30 strains of pathogenic bacteria were detected, with gram-negative bacteria accounting for 60%, gram-positive bacteria for 33.33%, fungi for 3.3% and tuberculosis bacteria for 3.3%. Pseudomonas aeruginosa, klebsiella pneumoniae, streptococcus pneumoniae, staphylococcus aureus accounted showed the highest proportion. Most of MM patients with pulmonary infection showed a heterprognosis after two weeks antibiotic treatment, while 3 patients died. About 30 percent of early deaths were due to pulmonary infections.@*CONCLUSION@#Anemia, neutropenia, ECOG score ≥2 points are the major clinical characteristics of the multiple myeloma patients with pulmonary infections. Pulmonary infection is an important cause of early death in patients with multiple myeloma. Pathogenic bacteria are mainly composed of gram-negative bacteria. Beta-lacta/ beta-lactamase inhibitor combinations or Carbapenems are effective empiric treatment for controlling the progression of pulmonary infection.

Value of Neutrophil/Lymphocyte Ratio and Monocyte/Lymphocyte Ratio in the Prognosis of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR) in the valuation prognosis of patients with multiple myeloma (MM).@*METHODS@#The clinical data of 82 patients with initially diagnosed MM admitted to Gansu Provincial People's Hospital was analyzed retrospectively. NLR and MLR were calculated based on blood routine results respectively. The optimal cut-off point of NLR and MLR was determined according to the ROC curve, and the patients were divided into the high NLR/MLR group and the low NLR/MLR group. The general data, biochemical indicators and prognosis of the patients in each groups were compared respectively. The prognostic significance of the high NLR/MLR group and the low NLR/MLR group in patients between different treatment regimens and different clinical characteristics were analyzed. Risk stratification was designed based on NLR and high MLR as two risk factors, and the effect of risk factors, on the prognosis of MM patients were compared.@*RESULTS@#ROC curve analysis determined that the optimal cut-off point of NLR was 3.1 (sensitivity 75%, specificity 70.7%) and the optimal cut-off point of MLR was 0.34 (sensitivity 83.3%, specificity 53.4%). The lactate dehydrogenase (LDH) and mean platelet volume (MPV) were correlated to NLR and MLR (P<0.05). There were no significant difference in age, sex, serum calcium (Ca), β @*CONCLUSION@#Elevated NLR and MLR are associated with poor prognosis in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.

Analysis of Risk Factors of Herpes Zoster in Patients with Multiple Myeloma Treated with Bortezomib / 中国实验血液学杂志

OBJECTIVE@#To explore and analyze the risk factors of herpes zoster in patients with multiple myeloma (MM) during the chemotherapy with bortezomib.@*METHODS@#Clinical data of 85 MM patients treated with bontizomib from January 2015 to January 2019 were selected and divided into case group and control group accroding to the occurred of herpes zoster. The clinical characteristic, treatment outcome and related factor of herpes zoster were retrospective analyzed.@*RESULTS@#Twenty of the 85 patients with MM treated with bortezomib developed herpes zoster occurred (23.5%). Single-factor analysis showed that age≥65 years, lymphocytopenia occurred before treatment, neutropenia occurred before treatment, ECOG score≥2, application of cyclophosphamide, absence of preventive antiviral therapy were associated with the genesis of herpes zoster (P＜0.05). Multivariate logistic regression analysis showed that lymphocytopenia occurred before treatment, the application of cyclophosphamide and the absence of preventive antiviral therapy were the independent risk factors for herpes zoster (P＜0.05).@*CONCLUSION@#The incidence of herpes zoster is high in the multiple myeloma patients treated with bortezomib. Lymphocytopenia occurred before treatment, the application of cyclophosphamide, and the absence of prophylactic antiviral therapy are the important risk factors for herpes zoster, for which the clinicians should attach great importance.

Inhibitory Effects of Agaricus Blazei Murrill (FA-2-b-β) on Proliferation of Chronic Myeloid Leukemia Cells in vivo and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigated the anti-tumor in vivo effect and mechanism of the acid RNA protein complex (FA-2-b-β) of Agaricus blazei Murrill extract.@*METHODS@#CCK-8 method was used to detected the inhibitory effect of FA-2-b-β on proliferation of primary CML cells from newly diagnosed CML patients, the CML mouse model was established by trail-venous injection of primary CML cells, and the survival time, blood cell count and body weight were observed, the immunoflouresence and immunehistochemistry analysis, RT-qPCR, Western bolt were used to detemine the expression of caspase-3 signal pathway-related apoptosis genes and proteins.@*RESULTS@#The experiments in vitro showed that the proliferative inhibitory rate in drug-treated group increased with concentration- and time-dependent manner (r@*CONCLUSION@#The FA-2-b-β can induce apoptosis of primary CML cells and prolong the survival time of CML model mouse, which may be related with the caspase-3 signal pathway related genes and proteins.

Primary Mechanisms of CD34CD38--KG1a Leukemia Stem Cells Apoptosis Induced by FA-2-b-β Extracted from Qinba Selenium- Mushroo / 中国实验血液学杂志

OBJECTIVE@#To investigate the apoptosis of CD34CD38-KG1a leukemia stem cells induced by Qinba selenium-mushroom extract(FA-2-b-β), and its related mechanism.@*METHODS@#CD34CD38--KG1a cells were isolated from KG1a cell line by magnetic activated cell sorting. The proliferation ability of KG1a stem cells treatd by various concentration of FA-2-b-β(1.2-2.4 mg/ml) in vitro for 24 and 48 hours were tested by cell counting Kit-8(CCK8). Flow cytometry was used to detect the apoptosis rate of KG1a stem cells in each group after treated by FA-2-b-β in vitro. Expression of BAX,BCL-2,Casepase-3 and Cyclin D1 protein were detected by Western blot.@*RESULTS@#The proportion of CD34CD38--KG1a stem cells was (95.35±2.63）% after immunomagnetic isolation. The proliferation of KG1a stem cells was inhibited significantly by FA-2-b-β, which shows a time- and dose-dependent manner (24 h,r=0.943; 48 h,r=0.976). Flow cytometry shows that with the increasing of drug concentration, the apoptosis was also increased, when KG1a stem cells was treated by FA-2-b-β for 24 h. Western blot indicated that the expression of apoptosis-related protein BAX and Casepase-3 were up-regulated, the expression of BCL-2 and Cyclin D1 were down-regulated.@*CONCLUSION@#FA-2-b-β can regulate proliferation and apoptosis KG1a stem cells, the involved mechanism may be related with the activation of mitochondrial-mediated apoptotic pathway.

Significance of Neutrophil/Lymphocyte Ratio in the Prognosis of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To study the value of neutrophil/lymphocyte ratio (NLR) in the evaluation of prognosis of patients with multiple myeloma (MM).@*METHODS@#NLR was calculated on the basis of the blood routine examination results of 65 patients with primary MM (MM group) and 83 persons receiving physical examination as control group, and the difference in 2 group was compared; moreover according to the median as threshold, the patients were divided into low NLR group (NLR＜2.34) and high NLR group (NLR≥2.34); the differences of age, sex, serum calcium β (Ca), microglobulin (β-MG), albumin (Alb), serum creatinine (Cr), hemoglobin (Hb), red blood cell distribution width (RDW) and lactate dehydrogenase (LDH) in 2 group were analyzed, and the survival rate was compared between the high and low-NLR group.@*RESULTS@#the NLR of MM patients was statistically significantly higher than that of the control group (z=-2.415, P＜0.05). Compared with the low NLR group, the β-MG and Cr levels of patients in the high NLR group seemed higher, but the difference was not statistically significant. The single-factor analysis showed that NLR, β-MG and Alb levels were risk factors for the prognosis of MM patients, and the multi-factor analysis showed that NLR and Alb level were independent risk factors influencing the prognosis of MM patients.@*CONCLUSION@#NLR elevation in patients with primary diagnosis of MM indicates a poor prognosis, which is an independent risk factor affecting the prognosis.

Effect of salidroside on apoptosis of bone marrow mesenchymal stem cells induced by ara-C / 中国实验血液学杂志

The purpose of this study was to investigate the effect of salidroside on human bone marrow mesenchymal stem cell (hBMMSC) apoptosis induced by cytarabine C (Ara-C) and its mechanism, hBMMSC were cultured in vitro and isolated by Fircoll density gradient centrifugation; cell surface antigens were measured by flow cytometry; the osteogenic and adipogenic differentiation of MSC was tested and evaluated by specific staining methods. The proliferation and apoptosis of cells exposed to Ara- C were detected by MTT and flow cytometry respectively. The experiments were divided into 4 groups: control group, Ara-C group, salidroside group and Ara-C+salidroside group. The mRNA expression of BCL-2 and BAX was assayed by RT-PCR. The results showed that the adherent cells displayed spindle and fibroblast cell-like shape; the hBMMSC expressed CD44, CD71 and HLA-ABC, not expressed CD34, CD45 and HLA-DR; the hBMMSC successfully differentiated into osteogenic and adipogenic lineages, which showed mineralization with von Kossa staining. Furthermore, liquid vacuoles were detected by oil red O staining; Ara- C exhibited a less inhibitory effect on the proliferation of hBMMSC treated with salidroside. The apoptosis of hBMMSC treated with salidroside were significantly higher as compared with control group (P < 0.05); RT-PCR results demonstrated that the BCL-2 expression was significantly down regulated but BAX mRNA expressions was up-regulated in Ara- C group as compared with those in the control group. Salidroside significantly inhibited the apoptosis of MSC and reversed the mRNA expression of BCL-2 and BAX. It is concluded that salidroside can inhibit the apoptosis of hBMMSC induced by Ara-C, its mechanism may be related with the regulation of BCL-2/BAX expression.

Outcome of endovascular stent graft placement in patients with acute thoracic aortic syndromes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the outcome of endovascular stent graft placement in patients with acute thoracic aortic syndromes.</p><p><b>METHODS</b>Emergency stent-graft implantations were performed in 57 patients with acute thoracic aortic syndromes from May 2001 to December 2005 (45 Stanford B aortic dissections, 9 acute penetrating aortic ulcers or pseudoaneurysms. 3 traumatic thoracic aneurysms). The clinical data, efficacy and follow-up results were analyzed.</p><p><b>RESULTS</b>Procedures were successful in all patients. Type I endoleaks were evidenced in 5 patients and ascending aortic dissection occurred in 1 patient during operation, 5 patients with acute penetrating aortic ulcer complicating with coronary artery disease received successful PCI immediately post endovascular stent graft placement. Adynamia in extremities occurred in 1 patient and recovered two days later post anisodamine and mcnicol treatments. Left vertebral artery ischemia was found in 1 patient due to coated subclavian artery by stent-graft and the patient recovered spontaneously after two days lethargy without special treatment. The mean ICU time after surgery was 3.5 days (1 - 8 days) and the mean hospitalization time was 10 days. The mean follow-up time was 25.30 +/- 13.1 months (1 - 47 months). Two patients died within 30 days after operation, 1 patient died of rupture of the ascending aortic dissection (7 days post operation), 1 patient died of acute renal failure at the 2nd day post operation. One patient died of empsyxis 3 months after procedure, 1 patient died at the 4th month post procedure for unknown reason, 1 patient received second stent-graft implantation because of a newly formed endoleak at the proximal end of the stent-graft, 5 patients received second stent-graft implantation because of newly formed leaks at the remote end of the stent-graft. No paraplegia or stent migration or stenosis was observed during the follow up period. Total mortality during hospitalization and follow-up was 7.0%.</p><p><b>CONCLUSION</b>Patients with acute thoracic aortic syndrome could be effectively and safely treated by coated stent-graft endovascular placement.</p>

Left atrial plication for left atrium associated with mitral valve disease / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effects of left atrial plication (LAP) in patients with giant left atrium (GLA) associated with mitral valve disease.</p><p><b>METHODS</b>Twenty-three patients with left atrial diameter (LAD) over 8.0 cm were enrolled. All cases underwent valve replacement and LAP between November 1993 and November 2004 were studied retrospectively. According to New York Heart Association (NYHA) classification, 15 belonged to class III, 8 to class IV. Mitral valve replacements were performed in 18 patients (mechanical valve in 17 and biological valve in 1), double value replacement in 5, tricuspid valve plasty (TVP) in 15, atrial fibrillation radiofrequency ablation in 2.</p><p><b>RESULTS</b>Low output syndrome happened in 3, respiratory failure in 2. The early death was in 3 cases (operative mortality 13%). The causes of death were: heart failure in 2 cases and stroke in 1. LAD was decreased significantly in patients after operation.</p><p><b>CONCLUSIONS</b>LAP has considerably beneficial effects on improvement of postoperative respiratory and cardiac function, reducing operative mortality. Atrial fibrillation radiofrequency ablation is effective in patients with GLA associated with valve disease. It may be recommended for patients with GLA during mitral valve surgery, especially for patients with LAD > 8.0 cm.</p>

Surgical management for Stanford A aortic dissection / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the surgical experience for Stanford A aortic dissection.</p><p><b>METHODS</b>Sixty-eight patients with Stanford A aortic dissection underwent surgery from March 1998 to October 2004, acute aortic dissection in 45 cases, chronic aortic dissection in 23 cases. The operation were performed by using moderate hypothermic cardiopulmonary bypass in 53 cases, deep hypothermic circulatory arrest (DHCA) and retrograde cerebral perfusion (RCP) in 11 cases; DHCA with antegrade selective cerebral perfusion (SCP) in 4 cases. Surgical procedures included ascending aortic grafting in 7 cases, ascending and hemiarch grafting in 6, ascending and total arch grafting in 3, ascending and total arch grafting with Frozen elephant trunk procedure in 4. Concomitant procedures included Bentall procedure in 34 cases, Wheat procedure in 12 cases, aortic valvuloplasty in 2 cases, mitral valvuloplasty in 1 cases. Urgent surgery was in 39 cases (emergency surgery in 19).</p><p><b>RESULTS</b>Operative mortality was 7% (urgent surgery mortality was 8%, elective surgery mortality was 7%). Fifty-eight cases were followed up for (37 +/- 22) months. Actuarial survival of 58 cases at 1, 3 and 5 years was 100%, 95% and 86% respectively.</p><p><b>CONCLUSION</b>The choice of surgical procedures depend on the location of intimal tear for Stanford A aortic dissection. Proper surgical indication, technique and brain protections are the key factors of Stanford A aortic dissection surgery.</p>

Clinical analysis of pregnancy and postpartum cardiovascular complications in Marfan syndrome / 中华妇产科杂志

Objective To investigate the management of pregnancy and cardiovascular complications in women with Marian syndrome(MFS).Methods From October 1994 to September 2006, 30 patients with MFS undergoing cardiovascular surgery were studied retrospectively.Results In the labor of 46 offsprings given birth by 30 women,5 cases(11%)were performed elective cesarean section because of the existence of aortic complication,and 12(26%)were diagnosed as MFS.The gestation in two patients was terminated due to deterioration of aortic abnormalities during their third trimester,and they received surgical treatment with Bcntall procedure.Two developed acute aortic dissection during labor and post delivery respectively.With the manipulation of anticoagulation peripartum,one who had the implantation with mechanical prosthesis went through pregnancy and delivery uneventfully.The average duration between delivery and cardiovascular surgery was(15?9)years.Conclusions Vaginal delivery can be done safely in patients with the MFS who do not have or have mild cardiovascular system abnormalities,aortic dissection,or other important cardiac abnormalities,cesarean section should be the preferred method of delivery.Women with MFS are at increased risk for dissection and congestive heart failure during pregnancy and should be counseled before pregnancy about these risks,as well as the inheritance of the condition.