OBJECTIVETo study the clinical significance of abnormal protein bands (APB) in multiple myeloma (MM) patients treated with bortezomib-based induction regimen and autologous stem cell transplantation (ASCT).

METHODSSixty-eight MM patients submitted to bortezomib-based induction therapy and ASCT from January 2007 to July 2012 were retrospectively studied. Monoclonal protein was detected by immunofixation electrophoresis (IFE).

RESULTSOf all 68 patients, 33 (48.5%) patients had APB. At the first emergence of an APB, two patients with light chain type achieved CR and before transplantation, and thirty-one patients were after transplantation with median time of 104 (ranged 33-404) days. The median duration of APB appearance was 105 (ranged 35-801) days. Patients who developed APB compared with those without APB, had a significantly higher CR plus very good partial response (VGPR) rates (100.0% vs 85.7%%, P=0.017) and CR rates (87.9% vs 62.9%) (P=0.03). There were no significant differences in gender, age, HGB, ALB, β2-microglobulin, M protein type, Durie-Salmon and ISS stages, the case number of first line or second line treatment, induction courses of bortezomib-based regimen, and the mode of ASCT. With a median follow-up of 33.4 (ranged 7.0-71.7) months, patients with APB tended to have a longer overall survival (OS) versus non-APB patients, although no significant difference obtained (P＞0.05). Among APB patients, OS was longer in patients whose appearance of APB occurred ＜6 months after transplantation than those ≥ 6 months, but the significant difference was not obtained yet (P＞0.05).

CONCLUSIONSPatients who developed APB had a significantly better response to bortezomib-based induction regimen followed ASCT. APB emergence has a good prognostic significance.

Adult ; Aged ; Boronic Acids ; therapeutic use ; Bortezomib ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; therapy ; Myeloma Proteins ; metabolism ; Prognosis ; Pyrazines ; therapeutic use ; Retrospective Studies ; Transplantation, Autologous

BACKGROUNDInternal metallic stents have been widely used in clinical practice, but a high postoperative restenosis rate limits its application. The purpose of this study was to determine the effect of intrabiliary radiation on muscle formation and biliary duct remodeling after biliary duct balloon injury in dogs.

METHODSTwenty male dogs (15 - 20 kg) were randomly divided into treatment group (n = 10) and control group (n = 10). Balloon overstretching injury was induced using a balloon catheter placed across the biliary duct. Subsequently, a 103Pd radioactive stent was positioned at the target site in each animal in the treatment group, providing the injured biliary duct with a radiation dose of 12.58 x 10(7) Bq. Dogs in the control group received Ni-Ti stents. All the dogs were killed one month after initial injury. The injured sections were dissected free from the dogs, and were processed for histological and morphological study. Cross-sections were stained with hematoxylin-eosin, Masson's trichrome, and Verhoef-van Giesen. Muscle formation area and lumen area were determined using a computer-assisted image analysis system.

RESULTSCompared with the control group, 103Pd radioactive stents significantly reduced muscle formation area (78.3%, P < 0.01), and percentage area of stenosis [control stents: (60.0 +/- 21.6)%, 103Pd radioactive stents: (31.6 +/- 9.5)%]. In addition, in the treatment group, the biliary duct lumen area was significantly larger than that in the control group (P < 0.01).

CONCLUSIONS103Pd radioactive stents providing a radioactive dose of 12.58 x 10(7) Bq are effective in reducing muscle formation and biliary duct remodeling after balloon overstretching injury.

Animals ; Bile Ducts ; pathology ; physiology ; radiation effects ; Catheterization ; adverse effects ; Dogs ; Male ; Muscle Development ; radiation effects ; Muscle, Smooth ; radiation effects ; Palladium ; administration & dosage ; Radioisotopes ; administration & dosage ; Random Allocation ; Stents ; adverse effects

Objective: To investigate the risk factors of chronic obstructive pulmonary disease (COPD) in Li and Han ethnic group in Hainan, China. Methods: All subjects were randomly selected from various regions in Hainan. General characteristics were compared between COPD cases and healthy control cases in both Li and Han ethnic groups. The odds ratio (OR), the corresponding 95% confidence interval (CI) of COPD were calculated by logistic regression. Results: A total of 277 Li COPD cases, 307 Li healthy control subjects, 290 Han COPD cases and 301 Han healthy control were included in this study. In both the Li and Han groups, the average age exceeded 65 years, and the cigarette number smoked per day and the smoking duration were correlated with risk of COPD. In the Li COPD subjects, low weight, smoking, and recurrent infection of respiratory tract were mainly risk factors; while the mainly risk factor of Han COPD subjects was family history of respiratory disease. Conclusions: The risk factors are different in COPD subjects of Han and Li nationalities in Hainan of China. The age and smoking are strongly correlated with COPD risk.

Objective To provide reference for the cold chain of stored RBCs on the sea by evaluating both blood containers containing phase-changed materials and the quality of stored RBCs during transportation.Methods In order to simulate blood supply on the sea,we transported the stored RBCs on land(100 min),on the sea(45 h)and stored them on the sea for another 7 days.The free hemoglobin(Hb), lactate dehydrogenase(LDH), and concentrations of K +and Na+were measured.Results The temperature of the blood container containing phase-changed materials rose from 4.1℃to 9.5℃.The contents of free Hb,K+and LDH were increased to(0.083 ±0.032)g/L,(15.097 ±1.791)mmol/L, and(106.00 ±17.83)U/L,respectively.During blood storage,the contents of the above three indices were increased to (0.111 ±0.035)g/L,(27.238 ±3.509)mmol/L and(227.00 ±111.94)U/L, while Na +decreased to(113.63 ± 4.012)mmol/L.Conclusion The temperature of the blood container containing phase-changed materials can be maintained at a constant temperature under more complicated environmental conditions,and the quality of the stored RBCs can be ensured.RBCs stored on the sea for more than 7 days are damaged more seriously than those stored on land.

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
Antineoplastic Combined Chemotherapy Protocols ; Bortezomib/therapeutic use* ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Multiple Myeloma/therapy* ; Retrospective Studies ; Stem Cell Transplantation ; Transplantation, Autologous ; Treatment Outcome

Aim To examine the neuroprotective im-pacts of total saponins from Trillium tschonoskii maxim(TST)on cerebral ischemia-reperfusion injury(CIRI)in rats and delve into the mechanisms of ferroptosis.Methods The CIRI model was prepared by dividing male SD rats into the model group,TST(0.1 g·kg-1)group,Donepezil hydrochloride(0.45 mg·kg-1)group,and sham group.The cognitive functions of rats in each group were assessed through the Morris water maze test,the changes in neurological function were evaluated using the Zea-Longa method,the infarct area was observed via TTC staining,and the pathologi-cal alterations in brain tissue were analysed using HE and Nissl staining.To further investigate the underly-ing mechanism,the mitochondrial structural changes were examined using transmission electron microscopy,and the levels of GSH-PX,MDA,and SOD were ana-lyzed.Additionally,the expressions of GPX4 and Nrf2 proteins were evaluated through immunohistochemistry and immunofluorescence.Furthermore,the protein lev-els of Keap1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways in rats were examined using Western blot-ting.Results The rats in the model group displayed diminished learning and memory capabilities in com-parison to those in the sham group,as well as a signifi-cantly increased cerebral infarction area and higher neurological function scores(P＜0.01),significantly increased cerebral infarct area,disordered and loosely arranged neurons,and reduced Nissl bodies.Addition-ally,mitochondria showed typical signs of ferroptosis.Changes related to ferroptosis included decreased activ-ities of SOD and GSH-PX(P＜0.01)and increased MDA levels(P＜0.01).The expression of GPX4 and Nrf2-positive cells was significantly reduced,along with decreased fluorescence intensity of GPX4.Further-more,the protein expression of Keap1,Nrf2,HO-1,GPX4,SLC7A11 in the hippocampus decreased(P＜0.05,P＜0.01).Following the administration of TST,these effects showed improvement.Conclusions TST has neuroprotective effects,enhancing learning and memory abilities while reducing oxidative stress levels.The mechanism may involve the inhibition of ferroptosis through the Keap-1/Nrf2/HO-1 and Nrf2/SLC7 A11/GPX4 pathways.

Aim To investigate the effects of total saponins from Trillium tschonoskii maxim(TST)on cognitive impairment and mitochondrial autophagy in aging rats induced by D-galactose(D-gal). Methods Male SD rats were randomly divided into normal control group,model group(D-gal,subcutaneous injection),intervention group(TST,low,medium and high dose groups by intragastric administration),with 10 rats in each group,and administered for 6 weeks. Morris water maze was used to evaluate the cognitive function. HE and Nissl staining were used to test the hippocampal and brain cortex morphology. Immunohistochemistry staining was applied to detect the localization expression of Pink1 and Parkin. Western blot was employed to detect the expressions of Pink1,Parkin,LC3-Ⅱ,p62 and Beclin1. Results Compared with the normal control group,the escape latency time was prolonged and the number of crossing platform decreased in D-gal model group(P<0.05). The number of neurons in hippocampus significantly decreased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly decreased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 were markedly reduced,while the expression of p62 was significantly raised(P<0.05). Compared with D-gal model group,the escape latency time of TST dose groups was shortened,the Times of crossing the platform was more,and the time of staying in the platform quadrant increased(P<0.05). The number of neurons in hippocampus significantly increased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly increased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 in hippocampus were apparently up-regulated,while the protein expression of p62 was evidently down-regulated(P<0.05). Conclusions TST has neuroprotective effects on the learning and memory capacities in aging rats induced by D-gal,which may be related to the increasing levels of Pink1,Parkin,LC3-Ⅱ and Beclin1 proteins and the activation of mitochondrial autophagy.

OBJECTIVETo investigate the potential signaling pathway that regulates the proliferation of human CD34cells stimulated by prostaglandin E2 receptor 4 agonist (EP4A) in vitro.

METHODSTwenty samples of peripheral blood containing stem cells were collected from the G-CSF mobilized healthy donors in our department of hematology. Human CD34cells were isolated by magnetic activated cell sorting (MACS) microbeads kit. The Cell Counting Kit-8 (CCK8) assay was used to determine the optimal concentration and time of EP4A to promote human CD34cell proliferation in vitro. Under the optimal condition, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect mRNA level of β-catenin, and Western blot was used to assay protein expression of β-catenin and P-GSK-3β in human CD34cells treated with EP4A.

RESULTSCulturing with 10 µmol/L EP4A for 72 h, it was found that EP4A promoted human CD34cell proliferation significantly, and the proliferation rate of human CD34cells was 1.36 times higher than that of the control(P=0.002). Under the optimal condition, it was also found that EP4A enhanced the β-catenin expression at both mRNA and protein levels, and up-regulated phosphorylation of GSK-3β in human CD34cells, but these effects could be inhibited by the EP4A antagonist EP4AA.

CONCLUSIONEP4A can enhance human CD34cell proliferation in vitro by activating Wnt/β-catenin signaling pathway.

Aging is a natural process accompanied with a progressive deterioration of cognitive functions. With an aging population, more and more elderly people are suffering from cognitive impairment. Previous studies have paid more attention to the impact of inflammation and oxidative stress on cognitive function during aging. Recently, it has been discovered that neurovascular coupling (NVC), a mechanism regulating cerebral blood flow, may play a significant role in aging-related cognitive impairment. NVC responses regulate the supply of energy substances and oxygen during brain activity, which in turn enhances cognitive function. However, as people grow older, NVC responses gradually weaken, which may be one of the mechanisms underlying aging-induced cognitive impairment. Given the important role of NVC responses in the brain, it is necessary to search for intervention methods that can improve NVC responses and promote cognitive function. Exercise is an effective means to delay aging and improve cognitive function. It also has a certain promoting effect on NVC responses. This article reviews the regulatory mechanisms of NVC responses, the relationship between NVC responses and cognitive function, and explores the effects of aging and exercise intervention on NVC responses, hoping to provide new research ideas for exercise intervention to improve NVC responses and promote cognitive function in the elderly.
Humans ; Aged ; Neurovascular Coupling/physiology* ; Aging ; Cerebrovascular Circulation/physiology* ; Cognition ; Brain

OBJECTIVE: To analyze the preservation effect and related influencing factors of human peripheral blood mononuclear cells under serum-free condition at 4 ℃. METHODS: Human peripheral blood mononuclear cells were isolated by density gradient centrifugation, and stored at 4 ℃ under different cell concentrations, supplemented with human serum albumin, and glucose. The cell viability, total cell number, viable cell number and cell phenotype were detected during preservation of 72 h. RESULTS: With the prolongation of storage time, the number of human peripheral blood mononuclear cells gradually decreased(r=0.982). Compared with the cell concentration of (5-6)×10⁶ cells/ml, the cell number decreased more slowly when the cell storage concentration was (1-2)×10⁶ cells/ml; Adding human serum albumin and glucose can effectively improve the survival rate of human peripheral blood mononuclear cells, among which 2% human serum albumin has a better preservation effect; Compared with the blank control group, the analysis results of cell subsets showed that the downward trends of NK cells and T cells were significantly slowed after adding albumin and glucose. CONCLUSION The cell density of (1-2)×10⁶/ml and 2% human serum albumin are more suitable for the preservation of PBMC, and 5% glucose can improve the preservation effect of human peripheral blood mononuclear cells at 4 ℃.
Humans ; Leukocytes, Mononuclear