Meta-Path Semantic and Global-Local Representation Learning Enhanced Graph Convolutional Model for Disease-Related miRNA Prediction.

Dysregulation of miRNAs is closely related to the progression of various diseases, so identifying disease-related miRNAs is crucial. Most recently proposed methods are based on graph reasoning, while they did not completely exploit the topological structure composed of the higher-order neighbor nodes and the global and local features of miRNA and disease nodes. We proposed a prediction method, MDAP, to learn semantic features of miRNA and disease nodes based on various meta-paths, as well as node features from the entire heterogeneous network perspective, and node pair attributes. Firstly, for both the miRNA and disease nodes, node category- wise meta-paths were constructed to integrate the similarity and association connection relationships. Each target node has its specific neighbor nodes for each meta-path, and the neighbors of longer meta-paths constitute its higher-order neighbor topological structure. Secondly, we constructed a meta-path specific graph convolutional network module to integrate the features of higher-order neighbors and their topology, and then learned the semantic representations of nodes. Thirdly, for the entire miRNA-disease heterogeneous network, a global-aware graph convolutional autoencoder was built to learn the network-view feature representations of nodes. We also designed semantic-level and representation-level attentions to obtain informative semantic features and node representations. Finally, the strategy based on the parallel convolutional-deconvolutional neural networks were designed to enhance the local feature learning for a pair of miRNA and disease nodes. The experiment results showed that MDAP outperformed other state-of-the-art methods, and the ablation experiments demonstrated the effectiveness of MDAP's major innovations. MDAP's ability in discovering potential disease-related miRNAs was further analyzed by the case studies over three diseases.

Clinical efficacy of comprehensive rehabilitation intervention and its effect on Quality of Life in patients with Advanced Liver Cancer after Ultrasound-guided Microwave Ablation.

Objective: To evaluate the clinical efficacy of comprehensive rehabilitation intervention and its effect on the quality of life (QoL) in patients with advanced liver cancer after ultrasound-guided microwave ablation (UMA). Methods: This is a retrospective study. Total 110 in-patients with advanced liver cancer who had received UMA in our hospital from January 2019 to January 2021 were included and randomly divided into two groups. Patients in the control group received the conventional intervention and those in the experimental group received comprehensive rehabilitation intervention. The incidence of postoperative complications as well as the differences in indicators, including emotional status, QoL score, and patient satisfaction before and after the intervention were analyzed and compared between the two groups. The differences in survival between the two groups were compared. Results: The incidence of postoperative complications in the experimental group was significantly lower than that of the control group. SAS and SDS scores of the experimental group were significantly decreased after intervention, while the control group had no significant change before and after intervention. KPS and SF-36 quality of life scores in the experimental group were significantly improved compared with the control group, and patient satisfaction was significantly higher than the control group, and the 12-month survival rate was significantly higher than that in the control group. Conclusion: Comprehensive rehabilitation intervention can reduce the incidence of postoperative complications, improve the mood and QoL, and increase patient satisfaction and survival rate in patients with advanced liver cancer after UMA.

A mini-review about direct steam heating and its application in dairy and plant protein processing.

The world's requirement for plant protein consumption is increasing. However, their application in different foods is limited due to their low techno-functionality. Heating is the most widely used method to improve the functionality of proteins. Compared to indirect tubular or plate heating methods, direct steam injection heating (DSIH) can heat the sample much faster, thus modifying the structure and functionality of protein differently. It is used in the sterilization of milk to minimize the heat-induced denaturation of whey proteins and the loss of volatiles. By contrast, its application in producing plant protein ingredients is seldom. This review summarizes recent research using DSIH to process dairy- and plant-based proteins and proposes future research perspectives. DSIH is a promising technique for producing functional protein ingredients. It is of particular interest to overcome the techno-functional hurdles of plant protein blends using DSIH to improve their behavior in different food matrices.

A novel nomogram to stratify quality of life among advanced cancer patients with spinal metastatic disease after examining demographics, dietary habits, therapeutic interventions, and mental health status.

BACKGROUND: It would be very helpful to stratify patients and direct patient selection if risk factors for quality of life were identified in a particular population. Nonetheless, it is still challenging to forecast the health-related quality of life among individuals with spinal metastases. The goal of this study was to stratify patient's populations for whom the assessment of quality of life should be encouraged by developing and validating a nomogram to predict the quality of life among advanced cancer patients with spine metastases. METHODS: This study prospectively analyzed 208 advanced cancer patients with spine metastases, and collected their general characteristics, food preferences, addictions, comorbidities, therapeutic strategies, and mental health status. The functional assessment of cancer therapy-general (FACT-G) and hospital anxiety and depression scale (HADS) were used to assess quality of life and mental health, respectively. The complete cohort of patients was randomly divided into two groups: a training set and a validation set. Patients from the training set were conducted to train and develop a nomogram, while patients in the validation set were performed to internally validate the nomogram. The nomogram contained significant variables discovered using the least absolute shrinkage and selection operator (LASSO) approach in conjunction with 10-fold cross-validation. The nomogram's predictive ability was assessed utilizing discrimination, calibration, and clinical usefulness. Internal validation was also completed using the bootstrap method after applying 500 iterations of procedures. A web calculator was also developed to promote clinical practice. RESULTS: Advance cancer patients with spinal metastases had an extremely low quality of life, as indicated by the average FACT-G score of just 60.32 ± 20.41. According to the LASSO and 10-fold cross-validation, Eastern Cooperative Oncology Group (ECOG) score, having an uncompleted life goal, preference for eating vegetables, chemotherapy, anxiety status, and depression status were selected as nomogram predictors. In the training set, the area under the receiver operating characteristic curve (AUROC) was 0.90 (95% CI: 0.84-0.96), while in the validation set, it was 0.85 (95% CI: 0.78-0.93). They were 0.50 (95% CI: 0.41-0.58) and 0.44 (95% CI: 0.33-0.56), respectively, for the discrimination slopes. The nomogram had favorable capacity to calibrate and was clinically useful, according to the calibration curve and decision curve analysis. When compared to patients in the low-risk group, patients in the high-risk group were above four times more likely to experience a poor quality of life (82.18% vs. 21.50%, P < 0.001). In comparison to patients in the low-risk group, patients in the high-risk group also exhibited significant higher levels of anxiety and depression. The webpage for the web calculator was https://starshiny.shinyapps.io/DynNomapp-lys/ . CONCLUSIONS: This study suggests a nomogram that can be applied as a practical clinical tool to forecast and categorize the quality of life among patients with spine metastases. Additionally, patients with poor quality of life experience more severe anxiety and depression. Effective interventions should be carried out as soon as possible, especially for patients in the high-risk group, to improve their quality of life and mental health condition.

Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution.

Lymphoma relapse is very common in clinical work, but lineage switch at relapse is rare. Although some cases have reported acute lymphocytic leukemia (ALL) switch to acute myeloid leukemia (AML) or myeloid sarcoma upon relapse, phenotype switch seldom occurs in other types of lymphoma. Here we report six cases with lineage switch from lymphoma to myeloid neoplasms. In our cohort, three cases were mantle cell lymphoma (MCL), and the other three cases were T-cell lymphoblastic lymphoma (T-LBL), B-cell lymphoblastic lymphoma (B-LBL), and diffuse large B-cell lymphoma (DLBCL) at the initial diagnosis. When linage switch occurred, most cases were AML M5 phenotypes, and only one case was myelodysplastic syndrome (MDS) phenotype. 11q23/mixed-lineage leukemia (MLL) rearrangement was negative in all cases. Although intensive therapy and stem cell transplantation have been applied in most cases, the poor outcome cannot be reversed. Therefore, we found that lineage switch could occur not only from ALL to AML or vice versa, but also from MCL or DLBCL to AML. Moreover, the incidence of MLL rearrangement in lineage switch is lower in adult hematologic malignancies as compared with pediatric patients.

UiO-66-NH2 nanocomposites incorporated cellulose acetate for forward osmosis membranes of high desalination performance.

In this paper, the hydrophilic UiO-66-NH2 nanomaterial was synthesized by the solvent-thermal method and characterized. Then, UiO-66-NH2 was introduced into the casting membrane solution of cellulose acetate (CA) forward osmosis (FO) membrane, and CA/UiO-66-NH2 forward osmosis membrane was prepared by the phase inversion method. The optimum preparation conditions of CA/UiO-66-NH2 mixed matrix membranes were determined as follows: the content of UiO-66-NH2 was 0.4 wt%, the coagulation bath temperature was 35°C, the mixing temperature was 50°C and the heat treatment temperature was 50°C. FTIR, SEM, water contact angle and AFM were carried out on CA/UiO-66-NH2 forward osmosis membrane prepared under the best preparation conditions. Compared to the CA forward osmosis membrane, the permeability and selectivity of the CA/UiO-66-NH2 membrane were improved. The water flux and reverse salt flux of the CA/UiO-66-NH2 forward osmosis membrane reached 52.32 L/(m2·h) and 2.43 g/(m2·h), respectively. The permeability selectivity of CA membranes and CA/UiO-66-NH2 membranes did not change much during 180 min, indicating that the two membranes had good long-term stability. This study shows a potential advantage of UiO-66-NH2 as additives for improvement in the desalination performance of forward osmosis membranes.

Investigation of the factors affecting foamability and foam stability of cold brew coffee.

BACKGROUND: In this study, the foamability and foam stability of nitrogen-infused cold brew coffee, as affected by coffee variety (Arabica and Robusta), degree of roast (light, medium, dark), brewing temperature (4, 20, 35 °C), brew ratio (1:5-1:15 w/w; coffee/water), ground particle size (712, 647 and 437 µm volume mean diameter) and beverage temperature (4, 20 and 35 °C), were investigated. RESULTS: Dynamic surface tension of cold brew, as determined from bubble tensiometry, decreased from 65-70 mN m-1 to about 60 mN m-1 as the bubble lifetime increased from 0.1 s to 1 s. Infusing the cold brew coffee (70 mL) with nitrogen gas for 30 s at 50 mL min-1 generated 30-40 mL of foam head. At the same degree of roast, brews prepared from Arabica beans had more stable foam than those from Robusta. Foam stability increased with increasing degree of roast, increasing brewing temperature, decreasing particle size, and decreasing the beverage temperature. By contrast, brew ratio had relatively less effect on foaming properties. Nitrogen-containing constituents present in the 80% (v/v) ethanol-soluble fraction (55.9% of total dissolved solids) of the brew samples were important contributors to foaming, while the 80% (v/v) ethanol-insoluble fraction (42.3% of total dissolved solids) that contained polysaccharides was important in stabilizing the foam. CONCLUSION: The foamability and foam stability of cold brew coffee are significantly affected by coffee variety, degree of roast, brewing temperature, ground particle size, and beverage temperatures. The foam properties are dictated by the low-molecular-weight nitrogen-containing compounds and high-molecular-weight polysaccharides present in the cold brew coffee. © 2022 Society of Chemical Industry.

Desalination Characteristics of Cellulose Acetate FO Membrane Incorporated with ZIF-8 Nanoparticles.

Forward osmosis membranes have a wide range of applications in the field of water treatment. However, the application of seawater desalination is restricted, so the research of forward osmosis membranes for seawater desalination poses new challenges. In this study, zeolitic imidazolate framework-8 (ZIF-8) was synthesized by a mechanical stirring method, and its crystal structure, surface morphology, functional group characteristics, thermochemical stability, pore size distribution and specific surface area were analyzed. The cellulose acetate (CA)/ZIF-8 mixed matrix forward osmosis membrane was prepared by using the synthesized ZIF-8 as a modified additive. The effects of the additive ZIF-8 content, coagulation bath temperature, mixing temperature and heat treatment temperature on the properties of the CA/ZIF-8 forward osmosis membrane were systematically studied, and the causes were analyzed to determine the best membrane preparation parameters. The structure of the CA membrane and CA/ZIF-8 mixed matrix forward osmosis membranes prepared under the optimal conditions were characterized by Fourier Transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), contact angle and Atomic force microscope (AFM). Finally, the properties of the HTI membrane (Membrane manufactured by Hydration Technology Innovations Inc.), CA forward osmosis membrane and CA/ZIF-8 mixed matrix forward osmosis membrane were compared under laboratory conditions. For the CA membrane, the water flux and reverse salt flux reached 48.85 L·m-2·h-1 and 3.4 g·m-2·h-1, respectively. The reverse salt flux and water flux of the CA/ZIF-8 membrane are 2.84 g·m-2·h-1 and 50.14 L·m-2·h-1, respectively. ZIF-8 has a promising application in seawater desalination.

Trypan blue removal from water with zein sorbents and laccase.

ABSTRACT: Zein-based materials were used to remove Trypan blue from water under flow conditions and in batch tests. In flow tests, zein dissolved at pH = 13 was injected in sand columns and subsequently coagulated with CaCl2, to create an adsorbent filter which removed over 99% of Trypan blue. Batch tests were conducted using zein powder, zein dissolved at pH = 13 and coagulated with CaCl2, Fe2Cl3 or citric acid, and zein dissolved in ethanol and then coagulated with water. The highest Trypan blue removal was achieved with zein powder (4000 mg Trypan blue/kg sorbent, as determined through spectrophotometry), followed by zein coagulated with Fe2Cl3 (500 mg Trypan blue/kg sorbent) and with other salts (140 mg Trypan blue/kg sorbent). Differences in the sorption efficiency are attributed to differences in the surface area. The sorption isotherm of Trypan blue onto zein-based sorbents was a Type II isotherm, suggesting physisorption. Desorption of Trypan blue was limited when zein-based coagulated sorbents were immersed in pure water. Trypan blue could be degraded by free laccase in water, as determined through spectrophotometry and electrospray ionization mass spectroscopy (ESI-MS). Trypan blue could also be degraded by laccase when zein-based laccase-containing sorbents were prepared at pH = 10, using Fe2Cl3 as coagulant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42452-020-04107-w.

Review of Analytical Methods to Detect Adulteration in Coffee.

As one of the most consumed beverages in the world, coffee plays many major socioeconomical roles in various regions. Because of the wide coffee varieties available in the marketplaces, and the substantial price gaps between them (e.g., Arabica versus Robusta; speciality versus commodity coffees), coffees are susceptible to intentional or accidental adulteration. Therefore, there is a sustaining interest from the producers and regulatory agents to develop protocols to detect fraudulent practices. In general, strategies to authenticate coffee are based on targeted chemical profile analyses to determine specific markers of adulterants, or nontargeted analyses based on the "fingerprinting" concept. This paper reviews the literature related to chemometric approaches to discriminate coffees based on nuclear magnetic resonance spectroscopy, chromatography, infrared/Raman spectroscopy, and array sensors/indicators. In terms of chemical profiling, the paper focuses on the detection of diterpenes, homostachydrine, phenolic acids, carbohydrates, fatty acids, triacylglycerols, and deoxyribonucleic acid. Finally, the prospects of coffee authentication are discussed.

Education level as a predictor of survival in patients with multiple myeloma.

BACKGROUND: Disparities in multiple myeloma (MM) prognosis based on sociodemographic factors may exist. We investigated whether education level at diagnosis influenced Chinese MM patient outcomes. METHODS: We performed a multicenter retrospective analysis of data from 773 MM patients across 9 centers in China from 2006 to 2019. Sociodemographic and clinical factors at diagnosis and treatment regimens were recorded, and univariate and multivariate analyses were performed. RESULTS: Overall, 69.2% of patients had low education levels. Patients with low education levels differed from those with high education levels in that they were more likely to be older, and a higher proportion lived in rural areas, were unemployed, had lower annual incomes and lacked insurance. Additionally, compared to patients with high education levels, patients with low education levels had a higher proportion of international staging system (ISS) stage III classification and elevated lactate dehydrogenase (LDH) levels and underwent transplantation less often. Patients with high education levels had a median progression-free survival (PFS) of 67.50 (95% confidence interval (CI): 51.66-83.39) months, which was better than that of patients with low education levels (30.60 months, 95% CI: 27.38-33.82, p < 0.001). Similarly, patients with high education levels had a median overall survival (OS) of 122.27 (95% CI: 117.05-127.49) months, which was also better than that of patients with low education levels (58.83 months, 95% CI: 48.87-62.79, p < 0.001). In the multivariable analysis, patients with high education levels had lower relapse rates and higher survival rates than did those with low education level in terms of PFS and OS (hazard ratio (HR) = 0.50 [95% CI: 0.34-0.72], p < 0.001; HR = 0.32 [0.19-0.56], p < 0.001, respectively). CONCLUSIONS: Low education levels may independently predict poor survival in MM patients in China.

Association between the ABO blood group and primary knee osteoarthritis: A case-control study.

BACKGROUND: Recent studies have suggested association between the ABO blood group and inflammation, which was a crucial pathological process of primary knee osteoarthritis. The aim of this study was to investigate the association between the ABO blood group and primary knee osteoarthritis â€‹and the severity of primary knee osteoarthritis evaluated by the Kellgren/Lawrence score, as well as the histopathologic association in a subgroup of patients. METHODS: We performed a retrospective review of patients with primary knee osteoarthritis that served as the case group â€‹and a random sampling of healthy blood donors that served as the control group. The severity of knee osteoarthritis at the first outpatient visit was evaluated by the Kellgren/Lawrence scoring system. Further study was performed to investigate the expression of blood group antigens in synovial tissue of the knee in both cases and controls. RESULTS: A total of 1126 cases and 30299 controls were involved. The proportion of AB blood group was higher in the case group than in the control group (9.7% vs. 7.8%), and logistic regression revealed that the AB blood group was a risk factor of primary knee osteoarthritis (P â€‹= â€‹0.025 and 0.048 for univariate and multivariate analysis, respectively), independent of age (P â€‹= â€‹0.973) and sex (P â€‹= â€‹0.520). Patients of the blood group AB had a higher Kellgren/Lawrence score (P â€‹= â€‹0.017). The immunohistochemical study indicated association between LeY antigen and primary knee osteoarthritis (P â€‹= â€‹0.029). CONCLUSIONS: This study suggested that the blood group AB was associated with primary knee osteoarthritis, as well as its radiological severity. Further study indicated that LeY antigen, which was related to the blood group, was associated with primary knee osteoarthritis. TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study revealed that blood group AB and LeY antigen was associated with primary knee osteoarthritis, which shed new light on the nature of osteoarthritis, and the development of novel therapy for osteoarthritis.

Investigation of the factors that affect the volume and stability of espresso crema.

This study investigated the effects of key brewing parameters (basket size, particle size, temperature, brewing ratio, coffee freshness, bean variety, and degree of roast) on the crema volume and stability of espresso coffees. Moreover, the brewing time and pressure, as well as brew total solid and extraction yield were characterized. The results show that the crema volume was mainly affected by the coffee variety and freshness. A larger crema volume was generated from Robusta than Arabica beans. Moreover, the fresher the coffee, the greater the crema volume. Crema stability was strongly affected by basket size, with double- and triple-shot baskets producing more stable crema than that from the single-shot basket. Arabica beans resulted in brews with a more stable crema than Robusta, attributable to the higher lipids content in the former. In comparison, crema volume and stability were less affected by the particle size, brewing ratio, and brewing temperature. Besides elucidating the parameters that affect the crema volume and stability of espresso coffee, findings from this study are expected to be useful for café barista and coffee connoisseurs in preparing espresso coffee with consistent crema quality.

Aberrant NEAT1_1 expression may be a predictive marker of poor prognosis in diffuse large B cell lymphoma.

BACKGROUND: Many studies have demonstrated that the long non-coding RNA (lncRNA), NEAT1_1, plays critical roles in various human tumor entities and is related to the survival of patients with malignancies. However, the role of NEAT1_1 in diffuse large B cell lymphoma (DLBCL) remains unclear. The aim of this study was to investigate the role of NEAT1_1 in DLBCL. METHODS: The expression of NEAT1_1 was evaluated in paraffin-embedded tissues from 64 DLBCL patients and 15 lymphnoditis patients using the ISH method. The correlations between the expression levels of NEAT1_1 and clinical-pathological features and patients' survival were also analyzed. After knocking down NEAT1_1 using shRNA in the DLBCL cell lines OCI-Ly1 and SUDHL-4, cell viability, apoptosis and migration were assessed by performing CCK8 assays, annexin V-FITC/PI double staining assays and migration filter assays, respectively. RESULTS: NEAT1_1 expression was increased in DLBCL tissue compared to lymphnoditis tissue samples (P< 0.001). The NEAT1_1 level was positively related to stage (P= 0.031), IPI (P= 0.017), extranodal site involvement (P= 0.042) and drug response (P= 0.040). Kaplan-Meier analysis showed that high expression levels of NEAT1_1 were correlated with a poor prognosis in DLBCL patients. After shRNA-NEAT1_1 was transfected into OCI-Ly1 and SUDHL-4 for 24 h, the NEAT1_1 level decreased to approximately one-third the level of the control. Moreover, the viability and migration ability of the DLBCL cell lines were significantly suppressed. shRNA-NEAT1_1 induced apoptosis in both DLBCL cell lines. CONCLUSIONS: Our results showed that NEAT1_1 plays an oncogenic role in DLBCL. NEAT1_1 expression may serve as a predictive marker for DLBCL patients.

Regulation of mPGES-1 composition and cell growth via the MAPK signaling pathway in jurkat cells.

Previous studies have suggested that microsomal prostaglandin E synthase-1 (mPGES-1) is highly expressed and closely associated with mitogen-activated protein kinase (MAPK) signaling pathways in various types of malignant cells. However, their expression patterns and function with respect to T-cell acute lymphoblastic leukemia (T-ALL) remain largely unknown. The present study investigated whether mPGES-1 served a crucial role in T-ALL and aimed to identify interactions between mPGES-1 and the MAPK signaling pathway in T-ALL. The results indicated that mPGES-1 overexpression in T-ALL jurkat cells was significantly decreased by RNA silencing. Decreasing mPGES-1 on a consistent basis may inhibit cell proliferation, induce apoptosis and arrest the cell cycle in T-ALL jurkat cells. Microarray and western blot analyses revealed that c-Jun N-terminal kinase served a role in the mPGES-1/prostaglandin E2/EP4/MAPK positive feedback loops. In addition, P38 and extracellular signal-regulated kinase 1/2 exhibited negative feedback effects on mPGES-1. In conclusion, the results suggested that cross-talk between mPGES-1 and the MAPK signaling pathway was very complex. Therefore, the combined regulation of mPGES-1 and the MAPK signaling pathway may be developed into a new candidate therapy for T-ALL in the future.

KPT-330 inhibition of chromosome region maintenance 1 is cytotoxic and sensitizes chronic myeloid leukemia to Imatinib.

As tyrosine kinase inhibitors (e.g., Imatinib, IM) fail to induce long-term response in some chronic myeloid leukemia (CML), novel therapies targeting leukemia-dysregulated pathways are necessary. Nuclear-cytoplasmic trafficking of proteins play a key role in the development of leukemia and drug resistance. KPT-330 (Selinexor), an inhibitor of chromosome region maintenance 1 (CRM1, nuclear receptor exportin 1, XPO1), demonstrated activities against a few hematological malignancies. We examined the anti-leukemic efficacy of KPT-330 in IM-resistant CML. Cell viability was examined by MTS assay. Apoptosis and cell cycle were assessed by flow cytometry. CRM1 mRNA was detected by PCR. Expression of CRM1 protein and its cargo proteins were determined by western blot or immunofluorescent staining. Furthermore, we engrafted nude mice subcutaneously with IM-resistant CML K562G. Mice were treated with IM, KPT-330 alone or in combination. Expression of CRM1 in CML were markedly higher than control. KPT-330 inhibited proliferation, induced cell cycle arrest and apoptosis of K562 and K562G. IC50 of IM on K562G was reduced by KPT-330. Mechanistically, KPT-330 inhibited CRM1 and increased the nuclear/cytoplasm ratio of BCR-ABL and P27. p-AKT was downregulated while p-STAT1 and caspase-3 were upregulated. Furthermore, KPT-330 showed anti-leukemic effect in primary IM-resistant CML with T315I mutation in CRM1-dependent manner. In K562G xenograft mice model, KPT-330 inhibited tumor growth and sensitized K562G to IM in vivo. To conclude, KPT-330 showed anti-leukemic activity and sensitized CML to IM in CRM1-dependent manner in vitro and in vivo. KPT-330 represents an alternative therapy for IM-refractory CML, warranting further investigation of CRM1 as therapeutic target.

[Expression of HMGB1 in Spleen of Adult Patients with Chronic and Refractory Immune Thrombocytopenia and Its Significance].

OBJECTIVE: To investigate the expression and clinical significance of high mobility group box 1(HMGB1) in spleen of adult patients with chronic and refractory immune thrombocytopenia(ITP). METHODS: Twenty chronic and refactory ITP patients received splenectomy were enrolled in ITP group and 20 cases of traumatic spleen rupture were enrolled in control group. The splenectomy efficacy in ITP patients was analyzed retrospectively. The HMGB1 expression in spleen tissue was detected by immunohistochemistry, and the correlation between different expression levels of HMGB1 and splenectomy efficacy were analysed. Meanwhile, the protein expression levels of HMGB1 in peripheral blood serum and mononuclear cells(PBMNC) of 25 patients with chronic and refractory ITP were detected by ELISA and Western blot. RESULTS: The median platelet count before splenectomy was 7.5 (0-20) ×109/L; all the patients showed that the initial response to splenectomy within the first month after operation was 100%, the median time of response was 1 day (1-6 days). The median peak platelet count post splenectomy was 448.5 (161-1272)×109/L. In the median time of 10(3-30) months, the platelets count in 8 patients was reduced to varying degrees. After a median follow-up of 69.5 months (22-195), complete response was found in 12 patients, 4 cases showed response and 4 did not. The HMGB1 expression positive rate in spleen of ITP patients was significantly higher than that in control group (85.0% vs 15.0%)(P<0.001). There were a negative correlation between the HMGB1 expression in ITP and therapeutic outcome after splenectomy (r=-0.791, P<0.01). In addition, HMGB1 expression levels in serum and PBMNC of the patients with chronic refractory ITP were also significantly higher than that in healthy controls (P<0.01). CONCLUSION: The splenectomy has been found to be effective therapeutic method for patients with ITP, the HMGB1 highly express in the spleen of the patients with chronic refractory ITP, but negatively correlats with the therapeutic outcome after splenectomy.

Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells.

Ribosomal S6 kinases (RSKs) are directly regulated by extracellular signal-regulated kinase (ERK) signaling and are implicated in cell growth, survival, motility and senescence. The present study observed that RSK1 was overexpressed in primary untreated leukemia patient bone marrow samples compared with the expression at the complete remission stage, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a high RSK1 expression (relative expression ≥10) was associated with a significantly shorter overall survival (P=0.038) compared with that in patients with low RSK1 expression (relative expression <10). The current study also investigated the effect of luteolin, a novel p90 ribosomal S6 kinase (RSK) inhibitor extracted from Reseda odorata L., which shows strong biochemical functions including anti-allergy, anti-inflammation and anti-cancer functions, in MOLM-13 and Kasumi-1 leukemic cells. The cell viability, apoptosis and migration ability analysis were assessed by performing a cell counting kit-8 assay, Annexin V-FITC/PI double staining and migration filter assay, respectively. The results indicated that luteolin inhibited the growth of the leukemic cell lines through induction of apoptosis, while the migration ability was also suppressed. Overexpression of RSK1 by plasmid transfection was found to decrease the luteolin-induced apoptosis and migration capabilities. By contrast, knockdown of the RSK1 expression by small interfering RNA appeared to induce the same effect as luteolin on MOLM-13 and Kasumi-1 leukemic cells. In conclusion, these results suggest that luteolin inhibits leukemic cell proliferation and induces apoptosis by inhibition of the RSK1 pathways.

[Effects of shRNA Targeting mPGES-1 on Tumorigenicity of K562 Cells in Nude Mice In Vivo].

OBJECTIVE: To investigate the effects of shRNA targeting mPGES-1 on tumorigenicity of human acute leukemia K562 cells in nude mice in vivo and its mechanisms. METHODS: For experiment 3 groups including KD group(expression of mPGES-1 in K562 cells was down-regulated by shRNA), CON (cells without any treatment) and NC group (cells treated with nonspecific-sequence shRNA) were set-up. Western blot was used to test the expression of ß-catenin and cyclinD1 in cells. Then the cells of 3 groups were implanted into BALB/c nude mice subcutaneously to establish murine xenograft model. The growth state of the mice and the size of the xenograft tumor were recorded. HE staining was used to observe the morphology of xenograft tumor. Expressions of ß-catenin and cyclinD1 in xenograft tumor were detected by immunohistochemical staining. RESULTS: In vitro the expression of ß-catenin and cyclinD1 in KD group were lower than the CON group and NC group (P<0.05). In vivo the tumor volume and weight of KD group were significant smaller than the other two groups (P<0.01). HE staining showed that tissues in the KD group were relatively looser in arrangement with smaller cell nucleus and less cytoplasm. The expression of ß-catenin and cyclinD1 in the KD group were remarkable weak as compared with that in CON group and NC group (P<0.05). CONCLUSION: Down-regulating the expression of mPGES-1 by shRNA may significantly inhibit the tumorigenicity of K562 cells in nude mice in vivo and its mechanism may be related with the inhibition of expression of ß-catenin and cyclinD1.