Establishment of a prediction model for disease progression within one year in newly diagnosed multiple myeloma patients.

Multiple myeloma is still an incurable disease In the past decade, with the continuous progress of treatment methods, the progression-free survival of patients has been prolonged, but some patients still progress in the early stage of the disease. Our research analyses the clinical laboratory indicators of newly diagnosed multiple myeloma (NDMM) patients, to obtain the relevant factors of disease progression within one year in MM patients and to establish a prediction model.108 MM patients treated in our hospital from January 2015 to January 2020 were retrospectively analyzed. After univariate and multivariate logistic regression analyses, the related factors of disease progression within one year in NDMM patients were obtained, and a prediction model was established.Treatment regimen containing at least two targeted drugs (OR = 0.226, 95% CI 0.068-0.753), increased lactate dehydrogenase(LDH, OR = 3.452, 95% CI 1.101-10.826) and increased serum corrected calcium(OR = 4.466, 95% CI 1.346-14.811) were identified as potential predictors by statistical analysis. The prediction model was obtained: x = -2.042-1.489 × treatment regimen (including at least two targeted drug assignment as 1, otherwise 0) + 1.239 ×LDH (U/L, lactate dehydrogenase elevation assignment as 1, normal as 0) +1.496 × serum corrected calcium (mmol/L, serum corrected calcium elevation assignment as 1, normal as 0). Receiver operating characteristic curve analysis showed that the model has good predictive performance.The possibility of disease progression within one year can be predicted by the prediction model. The model can be used as a reference for clinicians to make individualized treatment plans for patients so that patients can obtain better treatment effects.

Development and validation of a nomogram for steroid-resistance prediction in immune thrombocytopenia patients.

OBJECTIVES: Corticosteroid is first-line therapy in immune thrombocytopenia. However, nearly 30% of patients appear in steroid-resistance. Our research analyses the relevant indicators of patients and develops a risk prediction model to predict the poor response to steroid-therapy in ITP patients. METHODS: We collected data from 111 ITP patients admitted to Xiamen University Zhongshan Hospital from 2013 to 2019 as the training cohort and 65 ITP patients during 2019-2020 as the external validation cohort. Screening significant factors(P < 0.05) in univariate analysis, and further identified to be independent variables in multivariable logistic regression analysis. Incorporated the significant risk factors in and presented them with a nomogram based on independent risk predictors. The nomogram was assessed by receiver operating characteristics curves and decision curve analysis. RESULTS: We constructed a steroid-resistance prediction model based on the potential predictors including age, serum ferritin and expression of HBsAg. As a result, based on the area under the ROC curves, the training cohort (AUC: 0.718, 95% CI: 0.615-0.821) and the external validation cohort (AUC:0.799,95%CI:0.692-0.905), which displayed good discrimination. The decision curve showed that predicting the steroid-refractory risk in ITP patients using this nomogram with a range of the threshold probability between >16% and <70%. The nomogram appears good performance in predicting steroid-refractory ITP patients. CONCLUSION: Prediction model shows that elder patients with a high level of ferritin and positive expression of HBsAg may appear a high possibility of steroid-resistance. For these patients, TPO-RAs can be considered to help patients to get better treatment effects and develop a better health-related quality of life.

A tetravalent single chain diabody (CD40/HER2) efficiently inhibits tumor proliferation through recruitment of T cells and anti-HER2 functions.

Our aim was to construct a CD40×HER2 single chain diabody (ScDb) and determine its tumor-specific immune activation and anti-HER2 function. Overlap extension-polymerase chain reaction was applied in the construction of ScDb, and the protein was expressed with the pET28a (+)-Rosetta prokaryotic expression system. Soluble ScDb was purified by a nickel-nitrilotriacetic acid column. Dendritic cells (DC) was stimulated by ScDb and inhibited 4T1 cells proliferation in vitro. In 4T1 tumor mice model, lymphocyte infiltration was prominently detected in ScDb group, Caspase-3 expression was significantly upregulated. ScDb was labeled using quantum dots. Immunofluorescence assay indicated ScDb exhibited high affinity to HER2. T6-17 cells were inhibited by ScDb in vitro. The phosphorylation and expression levels of AKT, ERK were markedly decreased. In T6-17 tumor mice model. Compared to CD40 ScFv, HER2 ScFv and normal saline groups, tumor volume diminished significantly in ScDb group, and tumor cells showed extensive deformation, and pervasive karyopyknosis and karyorrhexis were found. In the present study, we successfully constructed a ScDb fragment and expressed it using a prokaryotic expression system. The in vivo and in vitro experimental results indicated that ScDb could inhibit the proliferation of tumor cells by stimulating the tumor-specific immunoreaction and blocking the HER2-related signaling pathway.

[Increased expressions of peripheral PD-1+ lymphocytes and CD4+CD25+FOXP3+ T cells in gastric adenocarcinoma patients].

Objective To detect the frequencies of peripheral programmed death-1+ (PD-1+) lymphocytes and CD4+CD25+FOXP3+ regulatory T cells in patients with gastric adenocarcinoma. Methods The study enrolled 29 patients with gastric adenocarcinoma and 29 age- and sex-matched healthy controls. Frequencies of PD-1+ lymphocytes and CD4+CD25+FOXP3+ regulatory T cells were detected using flow cytometry. Results The number of PD-1+ lymphocytes and CD4+CD25+FOXP3+ regulatory T cells in peripheral blood was higher in patients with gastric adenocarcinoma than that in the control group. Moreover, linear correlation analysis indicated a positive correlation between PD-1 expression and frequency of CD4+CD25+FOXP3+ regulatory T cells in peripheral blood of the patients. Conclusion Gastric adenocarcinoma patients present with increased PD-1+ lymphocytes and CD4+CD25+FOXP3+ regulatory T cells in the peripheral blood.

Current asthma control predicts future risk of asthma exacerbation: a 12-month prospective cohort study.

BACKGROUND: The performance of asthma control test (ACT) at baseline for predicting future risk of asthma exacerbation has not been previously demonstrated. This study was designed to explore the ability of the baseline ACT score to predict future risk of asthma exacerbation during a 12-month follow-up. METHODS: This post hoc analysis included data from a 12-month prospective cohort study in patients with asthma (n = 290). The time to the first asthma exacerbation was analyzed and the association between baseline ACT scores and future risk of asthma exacerbation was calculated as adjusted odds ratio (OR) using Logistic regression models. Further, sensitivity and specificity were estimated at each cut-point of ACT scores for predicting asthma exacerbations. RESULTS: The subjects were divided into three groups, which were uncontrolled (U, n = 128), partly-controlled (PC, n = 111), and well controlled (C, n = 51) asthma. After adjustment, the decreased ACT scores at baseline in the U and PC groups were associated with an increased probability of asthma exacerbations (OR 3.65 and OR 5.75, respectively), unplanned visits (OR 8.03 and OR 8.21, respectively) and emergency visits (OR 20.00 and OR 22.60, respectively) over a 12-month follow-up period. The time to the first asthma exacerbation was shorter in the groups with U and PC asthma (all P < 0.05). The baseline ACT of 20 identified as the cut-point for screening the patients at high risk of asthma exacerbations had an increased sensitivity of over 90.0% but a lower specificity of about 30.0%. CONCLUSION: Our findings indicate that the baseline ACT score with a high sensitivity could rule out patients at low risk of asthma exacerbations and predict future risk of asthma exacerbations in clinical practice.

[Study on the effect and mechanism of hypoxia on the histological structure of rat's lung].

UNLABELLED: OBJECTIVE; To observe the effect of intermittent normobaric hypoxia on the expression of transforming growth factor betal (TGF-beta1), Smad4, collagen I (Col I), tumor necrosis factor alpha (TNF-alpha) and on the changes in the histological structure of SPF SD Rat's lung. METHODS: Rats were placed in normal environment or intermittent normobaric hypoxia (101 kPa, 10% O2, 8 h every day) respectively. At the 3rd, 7th, 14th, 21st day, 5 rats from each group were killed and hematoxylin and eosin stain (HE stain) was applied to observe the pathological change in the lung of rats, immunohistochemical staining was used to detect the protein level of TGF-beta1, Col I. RT-PCR was performed to detect the mRNA levels of TGF-beta1 and Col I. Western blot to detect the expression of Smad4. Besides, the TNF-alpha in the bronchoalveolar lavage (BALF) were determined by ELISA. RESULTS: Results of HE stain demonstrated that the mild edema and inflammatory cell infiltration appeared in the lung tissue at the 3rd day, and gradually aggravated inflammation were observed as the treated time extended; meanwhile the interalveolar septum become thicker and thicker as the time of exposing to normobaric hypoxia increased. Compared with the normoxia group, not only the protein expression of TGF-beta1, Smad4 and Col I, but also the mRNA expression of TGF-beta1 and Col I were elevated (P < 0.01) in normobaric hypoxia group as the treatment time extended. Besides, a positive correlation (r = 0.944, P < 0.01) between the protein level of TGF-beta1 and Smad4 was observed and an up-regulated TNF-alpha in the BALF was also noticed. CONCLUSION: Normobaric hypoxia could cause pulmonary edema and inflammation by up-regulating expression of TNF-alpha, activating the TGF-beta1/Smads Signaling Pathway, and increasing the synthesization of Col I, the deposition of extracellular matrix as well as the interalveolar septum thickness.