Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Comparison of the performance of HPV DNA chip test and HPV PCR test in cervical cancer screening in rural China.

Background: This study aimed to evaluate the performance of two different principles of HPV testing in primary cervical cancer screening and ASC-US triage in rural areas. Methods: 3,328 and 3,913 women were enrolled in Shanxi, China in 2017 and 2018, respectively, and screened using liquid-based cytology and different HPV tests with a 4-year follow-up. Different screening methods commonly used in clinical practice were evaluated. Results: In the HPV PCR test cohort, the prevalence of HPV infection was 14.90%. A total of 38 cases of CIN2+ were identified at baseline, 2 of which were in the HPV-negative cohort and the rest in the HPV-positive cohort (2 = 186.85, p < 0.001). Fifty-three cases of CIN2+ were accumulated over 4 years. The HPV infection rate in the HPV DNA chip test cohort was 21.10%. A total of 26 CIN2+ cases were identified at baseline, all in the HPV-positive population (2 = 92.96, p < 0.001). 54 CIN2+ cases were cumulative over 4 years. At 4-year follow-up, HPV-negative results were significantly more protective against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) than normal cytologic results at baseline. HPV screening was more sensitive and specific than cytologic screening (using ASC-US as the threshold) and performed better on the HPV DNA microarray test. In addition, compared with HPV 16/18 testing, sensitivity increases and specificity decreases when using HPV testing for cytologic ASC-US triage, regardless of which HPV test is used. Conclusion: In the rural areas where we implemented the study, HPV tests performed well for screening than LBC and HPV DNA chip testing performed better than HPV PCR testing in the screening cohort. Optimal screening was achieved technically when used in combination with LBC for ASC-US population triage, without thinking the feasibility for resource availability.

Which is the preferred revision technique for loosened iliac screw? A novel technique of boring cement injection from the outer cortical shell.

STUDY DESIGN: An in vitro biomechanical cadaver study. OBJECTIVES: To evaluate the pull-out strength after 5000 cyclic loading among 4 revision techniques for the loosened iliac screw using corticocancellous bone, longer screw, traditional cement augmentation, and boring cement augmentation. SUMMARY OF BACKGROUND DATA: Iliac screw loosening is still a clinical problem for lumbo-iliac fusion. Although many revision techniques using corticocancellous bone, larger screw, and polymethylmethacrylate (PMMA) augmentation were applied in repairing pedicle screw loosening, their biomechanical effects on the loosened iliac screw remain undetermined. METHODS: Eight fresh human cadaver pelvises with the bone mineral density values ranging from 0.83 to 0.97 g/cm were adopted in this study. After testing the primary screw of 7.5 mm diameter and 70 mm length, 4 revision techniques were sequentially established and tested on the same pelvis as follows: corticocancellous bone, longer screw with 100 mm length, traditional PMMA augmentation, and boring PMMA augmentation. The difference of the boring technique from traditional PMMA augmentation is that PMMA was injected into the screw tract through 3 boring holes of outer cortical shell without removing the screw. On an MTS machine, after 5000 cyclic compressive loading of -200∼-500 N to the screw head, axial maximum pull-out strengths of the 5 screws were measured and analyzed. RESULTS: The pull-out strengths of the primary screw and 4 revised screws with corticocancellous bone, longer screw and traditional and boring PMMA augmentation were 1167 N, 361 N, 854 N, 1954 N, and 1820 N, respectively. Although longer screw method obtained significantly higher pull-out strength than corticocancellous bone (P<0.05), the revised screws using these 2 techniques exhibited notably lower pull-out strength than the primary screw and 2 PMMA-augmented screws (P<0.05). Either traditional or boring PMMA screw showed obviously higher pull-out strength than the primary screw (P<0.05); however, no significant difference of pull-out strength was detected between the 2 PMMA screws (P>0.05). CONCLUSIONS: Wadding corticocancellous bone and increasing screw length failed to provide sufficient anchoring strength for a loosened iliac screw; however, both traditional and boring PMMA-augmented techniques could effectively increase the fixation strength. On the basis of the viewpoint of minimal invasion, the boring PMMA augmentation may serve as a suitable salvage technique for iliac screw loosening.

Efficacy and safety of tocilizumab in COVID-19 patients.

In this retrospective study we assessed the efficacy and safety of tocilizumab in patients with critical or severe coronavirus disease 2019 (COVID-19). We enrolled 181 patients admitted to Huoshenshan Hospital (Wuhan, China) with confirmed COVID-19 between January 2020 and February 2020. Ninety-two patients were treated with tocilizumab, and 89 patients were treated conventionally. We analyzed the clinical manifestations, changes in CT scan images, and laboratory tests before and after tocilizumab treatment, and compared these results with the conventionally treated group. A significant reduction in the level of C-reactive protein was observed 1 week after tocilizumab administration. In some cases this meant the end of the IL-6-related cytokine storm. In addition, tocilizumab relieved fever, cough, and shortness of breath with no reported adverse drug reactions. These findings suggest tocilizumab improves clinical outcomes and is effective for treatment of patients with critical or severe COVID-19. However, future clinical trials are needed to better understand the impact of tocilizumab interference with IL-6 and provide a therapeutic strategy for treatment of COVID-19.

MiR-125a-5p inhibits the proliferation and invasion of breast cancer cells and induces apoptosis by targeting GAB2.

Objective: To investigate whether miR-125a-5p can inhibit the proliferation and invasion of breast cancer cells and induce apoptosis by targeting GAB2. Methods: qRT-PCR was used to detect the expression of miR-125a-5p in normal mammary epithelial cells and breast cancer cell lines; The miR-125a-5p overexpression plasmid was transiently transfected into MDA-MB-157 cells, and the proliferation, invasion and apoptosis of breast cancer cells were detected by CCK8 kit, Transwell chamber and flow cytometry, respectively; Gene silencing was used to knock down GAB2 gene in MDA-MB-157 cells, and the changes of proliferation, invasion, apoptosis and apoptosis-related proteins in breast cancer cells were detected by CCK8 kit, Transwell chamber, flow cytometry and western blot, respectively; The direct interaction between miR-125a-5p and GAB2 was detected by dual-luciferase reporter assay. The miR-125a-5p overexpression plasmid was transiently transfected into MDA-MB-157 cells, and the expression levels of GAB2 and apoptosis-related proteins were detected by western blot. Results: The expression of miR-125a-5p in breast cancer cell lines, MDA-MB-157 cells, MDA-MB-361 cells and MDA-MB-415 cells, was significantly lower than that in normal breast epithelial cells, MCF-10A cells; The proliferation and invasion ability of MDA-MB-157 cells transfected with miR-125a-5p were significantly inhibited, and the apoptosis rate was significantly increased; Since GAB2 knocked down, the proliferation and invasion ability of MDA-MB-157 cells were significantly inhibited, while the apoptosis rate was significantly increased, the Bax protein expression was significantly down-regulated, and the Bcl-2 protein expression was significantly up-regulated; The dual-luciferase reporter assay demonstrated that miR-125a-5p can specifically target GAB2. Transfected with miR-125a-5p, the GAB2 protein expression and Bax protein expression were significantly down-regulated, but the Bcl-2 protein expression was significantly up-regulated. Conclusion: miR-125a-5p inhibits the proliferation and invasion of breast cancer cells and induces their apoptosis by negatively regulating GAB2.

Expression, purification and epitope analysis of Pla a 3 allergen from Platanus acerifolia pollen.

Platanus acerifolia (P. acerifolia) is an important cause of pollinosis in cities. The use of allergen extracts on patients with allergic diseases is the most commonly applied method to attempt to treat pollinosis. Pla a 3, a non­specific lipid transfer protein, is a major allergen present in P. acerifolia pollen extracts. In the present study, the Pla a 3 gene was sub­cloned into a pSUMO­Mut vector using Stu I and Xho I sites and transformed into the Arctic Express™ (DE3) RP E. coli host strain. The purified Pla a 3 allergen was analyzed by western blotting and the results revealed that the Pla a 3 allergen has the ability to bind IgE in the P. acerifolia pollen of allergic patients' sera. Moreover, the authors predicted the potential B cell epitopes of the Pla a 3 allergen using the DNAStar Protean system, the Bioinformatics Predicted Antigenic Peptides system and the BepiPred 1.0 server. In addition, the T cell epitopes were predicted by the SYFPEITHI database and the NetMHCII­2.2 server. As a result, two B cell epitopes (35­45 and 81­86) and four potential T cell epitopes including 2­15, 45­50, 55­61 and 67­73 were predicted in the present study. The current results can be used to contribute to allergen immunotherapies and useful in peptide­based vaccine designs of pollen allergy.

Therapeutic implications of mesenchymal stem cells in acute lung injury/acute respiratory distress syndrome.

Acute lung injury (ALI), and its more severe form, acute respiratory distress syndrome (ARDS), are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. Current treatment of ALI/ARDS is primarily supportive, with lung protective ventilation and fluid conserving strategies. Despite improvement in these strategies, recent data indicate that the mortality of ALI/ARDS is still as high as 30 to 50%. Thus, there is a need for innovative therapies to further improve clinical outcomes of ALI/ARDS. Recent studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI/ARDS have shown promising results. This review focuses on existing studies that have tested the use of MSCs in models of ALI/ARDS, and the potential mechanisms underlying their therapeutic effects.

Self-assembled oligomeric procyanidin-insulin hybrid nanoparticles: a novel strategy for controllable insulin delivery.

Natural oligomeric procyanidin (OPC) with high biological and pharmacological activities was successfully used to synthesize OPC-insulin (OPC-INS) nanoparticles with different aggregation sizes for sustained and controlled delivery of hydrophilic insulin. The aggregation size of OPC-INS nanoparticles was regulated by OPC concentration, pH value, and incubation time. The fabrication mechanism would be that OPC and insulin self-assembled into a mixture of insulin aggregates via intermolecular interactions. In the self-assembly of insulin, OPC could serve both in the encompassing of insulin aggregates as a stabilizer and cross-linking different amounts of insulin aggregates into OPC-INS nanoparticles as interphase. OPC-INS nanoparticles not only demonstrated effective insulin drug loading but also exhibited aggregation-size-dependent and controlled insulin release performance in vitro. In the best case for OPC-INS nanoparticles, only ∼21% of insulin was released in 37 days. This study showed that the OPC-INS nanosystem is promising to serve as a long-acting insulin release formulation, and OPC has great potential as a drug carrier for nanomedicine.

Biomechanical effects of insertion location and bone cement augmentation on the anchoring strength of iliac screw.

BACKGROUND: Iliac screw loosening has been a clinical problem in the lumbo-pelvic reconstruction. Although iliac screws are commonly inserted into either upper or lower iliac column, the biomechanical effects of the two fixations and their revision techniques with bone cement remain undetermined. The purpose of this study was to compare the anchoring strengths of the upper and lower iliac screws with and without cement augmentation. METHODS: 5 pairs of formalin fixed cadaveric ilia with the bone mineral density values ranged from 0.82 to 0.97 g/cm(2) were adopted in this study. Using screws with 70-mm length and 7.5-mm diameter, 2 conventional iliac screw fixations and their revision techniques with cement augmentation were sequentially established and tested on the same ilium as follows: upper screw, upper cement screw, lower screw, and lower cement screw. Following 2000 cyclic compressive loading of -300 N to -100 N to the screw on a material testing machine, the maximum pull-out strengths were measured and analyzed. FINDINGS: The average pull-out strengths of upper, upper cement, lower, and lower cement screws were 964 N, 1462 N, 1537 N, and 1964 N, respectively. The lower screw showed significantly higher pull-out strength than the upper one (P=0.008). The cement augmentation notably increased the pull-out strengths of both upper and lower screws. The positive correlation between pull-out strength and bone mineral density value was obtained for the 4 fixations. INTERPRETATION: The lower iliac screw technique should be the preferred choice in lumbo-pelvic stabilization surgery; cement augmentation may serve as a useful salvage technique for iliac screw loosening; preoperative evaluation of bone quality is crucial for predicting fixation strength of iliac screw.

[Study on the relationship between polymorphisms of XPA gene and susceptibility of esophageal cancer].

OBJECTIVE: To explore the relationships between the polymorphisms of xeroderma pigmentosum A (XPA) and the susceptibility of esophageal cancer (EC), as well as its interaction with environmental factors-gene in Changzhi area, Shanxi province. METHODS: A case-control study was conducted, including 196 cases of EC and 201 controls. XPA 23G polymorphisms were determined with polymerase chain-restriction on fragment length polymorphism (PCR-RFLP). RESULTS: The risk of EC was significantly degraded in the individuals who had been carrying the XPA heterozygote (A/G) and mutation genotype (G/G), compared to those with wild genotype (chi2 = 16.21, P < 0.01) and the ORs were 0.58 (0.37-0.91) and 0.32 (0.18-0.56), respectively. There was negative interaction between XPA 23G mutation genotype and the consumption of pickled food (S = 0.04, API= -0.77). CONCLUSION: Genetic polymorphism in the XPA 23G might be associated with esophageal cancer in Changzhi area, and there was a negative action between XPA predisposing genotype and the consumption of pickled food.