Clinical Characteristics and Outcomes of AIDS-Related Burkitt Lymphoma in China: A Retrospective Single-Center Study.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) - related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy (P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [HR] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 (HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Construction and validation of prognostic scoring models to risk stratify patients with acquired immune deficiency syndrome-related diffuse large B cell lymphoma.

Acquired immune deficiency syndrome (AIDS)-related diffuse large B cell lymphoma (AR-DLBCL) is a rare disease with a high risk of mortality. There is no specific prognostic model for patients with AR-DLBCL. A total of 100 patients diagnosed with AR-DLBCL were enrolled in our study. Clinical features and prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by univariate and multivariate analyses. Central nervous system (CNS) involvement, opportunistic infection (OI) at lymphoma diagnosis, and elevated lactate dehydrogenase (LDH) were selected to construct the OS model; CNS involvement, OI at lymphoma diagnosis, elevated LDH, and over four chemotherapy cycles were selected to construct the PFS model. The area under the curve and C-index of GZMU OS and PFS models were 0.786/0.712; 0.829/0.733, respectively. The models we constructed showed better risk stratification than International Prognostic Index (IPI), age-adjusted IPI, and National Comprehensive Cancer Network-IPI. Furthermore, in combined cohort, the Hosmer-Lemeshow test showed that the models were good fits (OS: p = 0.8244; PFS: p = 0.9968) and the decision curve analysis demonstrated a significantly better net benefit. The prognostic efficacy of the proposed models was validated independently and outperformed the currently available prognostic tools. These novel prognostic models will help to tackle a clinically relevant unmet need.

Curcumin Elevates microRNA-183-5p via Cathepsin B-Mediated Phosphatidylinositol 3-Kinase/AKT Pathway to Strengthen Lipopolysaccharide-Stimulated Immune Function of Sepsis Mice.

Curcumin (Cur), a natural polyphenol compound, has been testified to modulate innate immune responses and also showed anti-inflammatory properties. Nevertheless, the mechanism was still poorly unknown, especially regarding Cur-modulated microRNAs (miRNAs) under the inflammatory response. CD39+ regulatory T cells (Tregs) were provided with distinct immunosuppressive action and exerted a critical role in the modulation of immune balance in sepsis. Nevertheless, the impact of Cur on the immune function of sepsis mice has not been reported. In this study, the influence of Cur on the inflammatory response and immune function of sepsis mice via augment of miR-183-5p and Cathepsin B (CTSB)-mediated phosphatidylinositol 3-kinase (PI3K)/AKT pathway was explored. Adoption of 20 mg/kg Cur was for gavage. In the meantime, injection of plasmid vectors of interference with miR-183-5p or CTSB was into the tail vein. Intraperitoneal injection of lipopolysaccharide (10 mg/kg) was to stimulate model of sepsis mice. Histopathological changes of sepsis mice were observed. The contents of tumor necrosis factor-α and Interleukin (IL)-1ß and IL-6 in serum of mice were examined. Detection of alanine aminotransferase, aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine in serum of mice was performed. Test of the percentage of CD39+ Tregs in tail venous blood of mice was implemented. Examination of miR-183-5p, CTSB, and PI3K/AKT was performed. The targeting of miR-183-5p and CTSB was detected. Cur was available to ameliorate the histological damage, to reduce the content of inflammatory factors, AST, and BUN, and to decline the percentage of CD39+ Tregs in tail venous blood of sepsis mice. Elevated miR-183-5p or silenced CTSB was available to further enhance the protection of Cur. Cur was available to accelerate miR-183-5p, which negatively modulated CTSB and Cur-mediated PI3K/AKT pathway via the miR-183-5p/CTSB axis to restrain inflammation of sepsis mice and enhance its immune function.

Jian-Pi-Bu-Xue-Formula Alleviates Cyclophosphamide-Induced Myelosuppression via Up-Regulating NRF2/HO1/NQO1 Signaling.

Jian-pi-bu-xue-formula (JPBXF), a TCM formula composed of twelve Chinese medicinal herbs, has been used in clinic to ease patients' state of weakness and fatigue especially after receiving anti-tumor chemotherapy in China. The lack of the phytochemical characterization, detail therapeutic evaluation and mechanism of JPBXF remains the main limitation for its spreading. In this study, we systematically evaluated the effectiveness and underline mechanism of JPBXF on cyclophosphamide (CTX)-induced myelosuppression and identified the main constituents of JPBXF aqueous extract. JPBXF treatments reversed CTX-induced myelosuppression through increasing the number of haematopoietic stem cells (HSCs) and expression of C-kit in bone marrow cells. Simultaneously, JPBXF treatments alleviated CTX-induced blood cells reduction by increasing numbers of RBCs and WBCs and levels of GM-CSF, TPO and EPO in plasma. JPBXF treatments reduced CTX-induced immunosuppression by increasing expressions of CD3, CD4, and CD8a in PBMCs, and recovering structure damages of thymus and spleen. Moreover, JPBXF notably increased the expression of NRF2 compared with CTX group, and subsequently up-regulated HO1 and NQO1 both in mRNA and protein levels. In addition, eighteen compounds were recognized from JPBXF aqueous extract and the potential targets of the identified compounds were predicted. Overall, JPBXF can greatly reverse CTX-induced myelosuppression in C57BL/6 mice, especially in improving the blood and immune function through activating NRF2/HO1/NQO1 signaling pathway, which provides a reliable reference for JPBXF application in clinical. By recognizing eighteen compounds in JPBXF aqueous extract and predicting the underline mechanisms of the identified compounds, our study would provide theoretical guidance for further research of JPBXF.

Mechanism of Cxc Chemokine Ligand 5 (CXCL5)/Cxc Chemokine Receptor 2 (CXCR2) Bio-Axis in Mice with Acute Respiratory Distress Syndrome.

BACKGROUND Acute respiratory distress syndrome (ARDS) is a common acute and severe disease in clinic. Recent studies indicated that Cxc chemokine ligand 5 (CXCL5), an inflammatory chemokine, was associated with tumorigenesis. The present study investigated the role of the CXCL5/Cxc chemokine receptor 2 (CXCR2) bio-axis in ARDS, and explored the underlying molecular mechanism. MATERIAL AND METHODS The pathological morphology of lung tissue and degree of pulmonary edema were assessed by hematoxylin-eosin staining and pulmonary edema score, respectively. Real-time PCR and Western blot analysis were performed to detect the expression levels of CXCL5, CXCR2, Matrix metalloproteinases 2 (MMP2), and Matrix metalloproteinases 9 (MMP9) in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression levels of CXCL5 and inflammatory factors (IL-1ß, IL-6, TNF-alpha, and IL-10) in serum. RESULTS The results demonstrated that diffuse alveolar damage and pulmonary edema appeared in lipopolysaccharide (LPS)-induced ARDS and were positively correlated with the severity of ARDS. In addition, CXCL5 and its receptor CXCR2 were overexpressed by upregulation of MMP2 and MMP9 in lung tissues of ARDS. In addition, CXCL5 neutralizing antibody effectively alleviated inflammatory response, diffuse alveolar damage, and pulmonary edema, and decreased the expression levels of MMP2 and MMP9 compared to LPS-induced ARDS. CONCLUSIONS We found that CXCL5/CXCR2 accelerated the progression of ARDS, partly by upregulation of MMP2 and MMP9 in lung tissues with the release of inflammatory factors.

A new 3D printed titanium metal trabecular bone reconstruction system for early osteonecrosis of the femoral head.

Presently, biomechanical support therapy for the femoral head has become an important approach in the treatment of early osteonecrosis of the femoral head (ONFH). Previous studies have reported that the titanium metal trabecular bone reconstruction systems (TMTBRS) achieved satisfactory clinical results for the treatment of early femoral head necrosis. Electron beam melting technology (EBMT) is an important branch of 3D printing technology, which enables the construction of an interface that is required for support of bone in-growth. However, the effect of TMTBRS created using EBMT for clinical applications for early ONFH is still unknown. At present, there are no reports on this topic worldwide. The purpose of this study was to assess the safety of a new 3D printed TMTBRS implant and to evaluate its clinical efficacy in early ONFH.Thirty patients who underwent surgery for ONFH were selected. The stages of ONFH were classified according to the Association Research Circulation Osseus (ARCO) classification. They were followed-up and radiological examination was performed at 6, 12, and 24 months post-surgery to assess TMTBRS stability and bone growth in the bone trabecular holder portion surface. To evaluate hip function, postoperative Harris and Visual Analogue Scale (VAS) scores were used.The postoperative Harris score increased significantly and VAS score decreased significantly at the 12-month follow-up compared to the 24-month follow-up, wherein the Harris score declined slightly and the VAS score was slightly elevated with the aggravation of ONFH. With the passage of time, postoperative improvement rates were 100% for IIA, 70% for IIB, and 0% for IIC. Hip-preserving rates were 100% for IIA, 100% for IIB, and 50% for IIC.The effect of TMTBRS treatment for early ONFH in ARCO IIA and ARCO IIB is satisfactory. However, it is not recommended for a relatively large area of necrosis such as in ARCO IIC.

Effect of blood biochemical factors on nontraumatic necrosis of the femoral head : Logistic regression analysis.

OBJECTIVE: This case-control study aimed to identify the risk factors of nontraumatic necrosis of the femoral head (NONFH). METHODS: In all, 242 patients with NONFH treated at the hip disease research center of our hospital between March 2012 and October 2015 were included. After excluding 19 patients with tumor or tuberculosis, 223 patients were enrolled. Controls comprised 223 healthy persons selected from our hospital database. Single-factor variance analysis and t test were performed to select the index of statistical significance. The 95% confidence interval (95% CI) and normal range of the selected indicators were compared, and abnormal related indexes were selected from the femoral head necrosis group. The selected indicators were based on the increase or decrease to locate the risk indicators and render their corresponding assignment. Logistic regression analysis of the risk factors was performed after the assignment. RESULTS: The necrotic group of patients with decreased carbon dioxide combining power (CO2CP), increased total cholesterol, increased low-density lipoprotein, and decreased high-density lipoprotein levels had statistically significant partial regression coefficient values and the odds ratios were 73.5 (95% CI 24.59-219.74), 7.15 (3.51-14.85), 633.07 (121.7-3304.78), and 20.11 (9.36-43.8), respectively, indicating that these are strong risk factors for NONFH. CONCLUSIONS: Abnormal lipid metabolism is a strong risk factor of NONFH. Lipid examination can be used as a screening tool for NONFH in high-risk populations, for alcoholism, and many hormone applications. The decreased CO2CP was associated with NONFH, and bone microcirculation was considered to possibly lead various conditions such as ischemia and hypoxia-related bone metabolic acidosis. However, further study is needed.

An Improved Variant of Soybean Type 1 Diacylglycerol Acyltransferase Increases the Oil Content and Decreases the Soluble Carbohydrate Content of Soybeans.

Kinetically improved diacylglycerol acyltransferase (DGAT) variants were created to favorably alter carbon partitioning in soybean (Glycine max) seeds. Initially, variants of a type 1 DGAT from a high-oil, high-oleic acid plant seed, Corylus americana, were screened for high oil content in Saccharomyces cerevisiae Nearly all DGAT variants examined from high-oil strains had increased affinity for oleoyl-CoA, with S0.5 values decreased as much as 4.7-fold compared with the wild-type value of 0.94 µm Improved soybean DGAT variants were then designed to include amino acid substitutions observed in promising C. americana DGAT variants. The expression of soybean and C. americana DGAT variants in soybean somatic embryos resulted in oil contents as high as 10% and 12%, respectively, compared with only 5% and 7.6% oil achieved by overexpressing the corresponding wild-type DGATs. The affinity for oleoyl-CoA correlated strongly with oil content. The soybean DGAT variant that gave the greatest oil increase contained 14 amino acid substitutions out of a total of 504 (97% sequence identity with native). Seed-preferred expression of this soybean DGAT1 variant increased oil content of soybean seeds by an average of 3% (16% relative increase) in highly replicated, single-location field trials. The DGAT transgenes significantly reduced the soluble carbohydrate content of mature seeds and increased the seed protein content of some events. This study demonstrated that engineering of the native DGAT enzyme is an effective strategy to improve the oil content and value of soybeans.

Optimized Animal Model of Cyclophosphamide-induced Bone Marrow Suppression.

Myelosuppression is one of the serious side effects of anticancer chemotherapeutic drugs that deteriorate the bodily functions of patients, thereby affecting the quality of life considerably. Prevention of myelosuppression in anticancer chemotherapy is an important research topic. A stabilized chemotherapy-induced myelosuppression animal model is necessary in experimental research. This study aimed to establish an optimized animal model of chemotherapy-induced bone marrow suppression. After C57BL/6 mice were treated with intermediate- and high-dose (25/50 mg/kg) cyclophosphamide (CTX) for 10 days, the body-weight, changes in thymus and spleen, number of white blood cells (WBCs), red blood cells (RBCs), and platelets (PLTs) and changes in bone marrow in the mice were systematically evaluated at the next 2, 7 and 14 days. Our results demonstrated that CTX treatments could significantly decrease the body-weight of mice, as well as the ratios of the weights of thymus and spleen to body-weight. The physiological structures of thymus and spleen were destroyed by CTX treatments. The number of WBCs and RBCs significantly declined after CTX treatments; however, the number of PLTs increased. Moreover, the expression of Sca1 in bone marrow cells decreased on Day 2 but increased on Day 14. The expression of CD34 decreased in bone marrow cells after CTX treatments. In conclusion, mice models, with high-dose CTX treatments for 10 days, can be an optimized animal model for chemotherapy-induced bone marrow suppression.

[Comparison of the efftec between eccentric fixation and intramedullary fixation for treatment of intertrochanteric fractures].

OBJECTIVE: To compare the efficacy between eccentric fixation and internal fixation for treatment of intertrochanteric fractures of femur,to provide a theoretical basis for the selection of the treatment method of the intertrochanteric fractures of femur. METHODS: From February 2007 to January 2010,82 patients with femoral intertrochanteric fracture were treated by internal fixation including 39 cases of eccentric fixation involving 23 males and 6 females, aged from 41 to 81 years old with an average of (62.68±10.69), using the DHS or proximal femoral locking plate; 43 cases of intramedullary fixation involving 15 males, 28 females,aged from 43 to 78 years old with an average of (62.60±8.37),using PFN or PFNA fixed. The surgical incision length, operative time, blood loss and postoperative Harris score between two groups were compared. RESULTS: The wound of two groups were primary healing without operative complications. All cases received follow-up for an average time of 18.3 months (12 to 28 months). The incision length, operative time and blood loss had a statistically significant difference between two groups (P<0.05). Harris scores of hip joint function at 1 month after operation had statistically significant difference between two groups (P<0.05), and Harris scores at 12 months after operation had no statistical significance difference between two groups. The rate of excellent and good was 89.7% in eccentric fixation group and 90.7% in intramedullary fixation group,the difference was not statistically significant (t=0.0613, P>0.05). In eccentric fixation group, there was 1 case of fracture nonunion with DHS loose and ensuing hip varus deformity. In intramedullary nail fixation group, there was no anti-rotation out,distal intramedullary nail of femoral refracture occurred in 1 case. CONCLUSION: Two treatment methods for the treatment of femoral fractures had a good therapeutic effect,but the intramedullary fixation had shorter operative time and less blood loss than the eccentric fixation,it prior to apply to osteoporosis and unstable femoral intertrochanteric fractures.

Effect of surfactant protein A on lipopolysaccharide-induced tumor necrosis factor-α expression in human proximal tubular epithelial cells.

BACKGROUND: Surfactant protein A (SP-A) contributes to the regulation of sepsis-induced acute lung injury. In a previous study, we demonstrated the expression and localization of SP-A in the kidneys. The present study evaluated the effect of SP-A on lipopolysaccharide (LPS)-induced tumor necrosis factor-a (TNF-α) expression and its underlying mechanisms in the human renal tubular epithelial (HK-2) cells. METHODS: Indirect immunofluorescence assay was used to detect SP-A distribution and expression in HK-2 cells. HK-2 cells were treated with various concentrations of LPS (0, 0.1, 1, 2, 5, and 10 mg/L) for 8 hours and with 5 mg/L LPS for different times (0, 2, 4, 8, 16, and 24 hours) to determine the effects of LPS on SP-A and TNF-α expression. Then, HK-2 cells were transfected with SP-A siRNA to analyze nuclear factor κB (NF-κB) P65 and TNF-α expression of HK-2 cells after LPS-treatment. RESULTS: Indirect immunofluorescence assay revealed that SP-A is localized to the membrane and cytoplasm of HK-2 cells. Interestingly, SP-A1/SP-A2 and TNF-a expression were found to be significantly increased in HK-2 cells upon LPS treatment. Transfection of LPS-treated HK-2 cells with SP-A siRNA resulted in significant increases in the levels of NF-κB P65 protein and TNF-α mRNA and protein compared to those in non-transfected LPS-treated HK-2 cells. CONCLUSION: SP-A plays an important role in protecting cells against sepsis-induced acute kidney injury by inhibiting NF-κB activity to modulate LPS-induced increase in TNF-α expression.