Publications by authors named "Rong Fu"

493 Publications

Predictive Role of Immune Profiling for Survival of Multiple Myeloma Patients.

Authors:
Liu Zhaoyun Fu Rong

Front Immunol 2021 5;12:663748. Epub 2021 Jul 5.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.

Despite new efficacy drugs and cell therapy have been used for multiple myeloma (MM) patients, some patients will relapse over time. We wonder the immune system play a vital role as well as MM cell during the development of disease. It is clear that the characteristic of myeloma cell is associated with the survival of MM patients. However, the link between the immune profiling and the prognosis of the disease is still not entirely clear. As more study focus on the role of immunity on multiple myeloma pathogenesis. There are plenty of study about the predictive role of immunity on the survival of multiple myeloma patients. Up to mow, the majority reviews published have focused on the immunotherapy and immune pathogenesis. It is indispensable to overlook the predictive role of immunity on multiple myeloma patients. Here, we give a review of vital previous works and recent progress related to the predictive role of immune profiling on multiple myeloma, such as absolute lymphocyte count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocytes and cytokines.
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http://dx.doi.org/10.3389/fimmu.2021.663748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287504PMC
July 2021

MRPL13 Act as a Novel Therapeutic Target and Could Promote Cell Proliferation in Non-Small Cell Lung Cancer.

Cancer Manag Res 2021 12;13:5535-5545. Epub 2021 Jul 12.

Department of Respiratory Medicine, Affiliated Hospital of Shandong University of Chinese Medicine, Jinan, People's Republic of China.

Background: The latent involvement of MRPL13 in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to explore the role of MRPL13 in NSCLC.

Methods: All analyses were performed in R software 4.0, SPSS version 23, and GraphPad Prism 8. The "limma" package was used to identify differentially expressed genes. Univariate and multivariate cox analyses were used to identify prognosis-related genes. A549 and H1299 lung cancer cell lines were selected for phenotypic experiments.

Results: The high level of MRPL13 was correlated with poor T classification and overall survival. In vitro experiments showed that MRPL13 was highly expressed in NSCLC tissue and cell lines. MRPL13 knockdown inhibited the proliferation of lung cancer A549 and H1299 cell lines, which was further validated by in vivo experiment. Moreover, GSEA analysis suggested that the pathway of MYC target, PI3K/AKT/mTOR/ signaling, oxidative phosphorylation, and G2/M checkpoints may be the potential pathway where MRPL13 was involved. Meanwhile, MRPL13 demonstrated a negative correlation with M1 macrophage, CD8+ T cells, and CD4+ T cells, making it an underlying immunotherapy target of NSCLC.

Conclusion: MRPL13 may promote the proliferation of NSCLC cells and serve as an independent tumor marker and an emerging therapeutic target.
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http://dx.doi.org/10.2147/CMAR.S316428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285246PMC
July 2021

Advances in the creation of animal models of paroxysmal nocturnal hemoglobinuria.

Hematology 2021 Dec;26(1):491-496

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

Paroxysmal nocturnal hemoglobinuria (PNH) is a disease caused by a phosphatidylinositol glycan anchor biosynthesis class A () mutation in hematopoietic stem cells. There are three theories about the possible mechanism of the pathogenesis of PNH: immune escape, anti-apoptotic mechanism, and secondary gene mutation. There has been little gain in the knowledge regarding its pathogenesis during the last decade owing to the lack of representative cell lines and animal models. There have been recent reports about the successful creation of PNH mouse and PNH rhesus macaque models. The detection of glycosylphosphatidylinositol-anchor protein (GPI-AP)-deficient cells and/or fluorescently labeled variant of aerolysin (FLAER) test, estimation of erythrocyte life span, and hemolysis-related experiments demonstrated that these animal models of PNH had GPI-AP-deficient blood cells with shortened lifespans and increased sensitivity to complement-activated hemolysis. However, there were no clinical manifestations such as hemolysis and thrombosis in these animal models. This suggested that the mutation is one of the several conditions required for PNH, but it alone is not enough to cause PNH.
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http://dx.doi.org/10.1080/16078454.2021.1945244DOI Listing
December 2021

Upregulated Expression of Profilin1 on Dendritic Cells in Patients With Severe Aplastic Anemia.

Front Immunol 2021 16;12:631954. Epub 2021 Jun 16.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.

Severe aplastic anemia (SAA) is a life-threatening form of bone marrow failure that is associated with very high mortality. Dendritic cells (DCs) are antigen presenting cells (APCs) with powerful movement ability, which is an important factor affecting immune function. The expression of profilin1 (Pfn1) plays an important role in the regulation of cell movement ability. We detected the expression of Pfn1 mRNA in the bone marrow (BM) myeloid dendritic cells (mDCs) from patients with SAA using RT-PCR. Next, we examined Pfn1 expression on mDCs using flow cytometry (FCM). We also assessed the relationship between Pfn1 expression and cytokine levels. Our data showed increased Pfn1 mRNA expression in patients with SAA. The expression of Pfn1 in BM mDCs increased in SAA patients. The expression of Pfn1 on mDCs and cytokines (TNF-α and IFN-γ) were positively correlated in the serum of untreated patients with SAA. Taken together, we found that the expression of Pfn1 on mDCs of SAA patients increased, which may affect the function of mDCs. Profilin 1 may be involved in the immunopathogenesis of SAA.
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http://dx.doi.org/10.3389/fimmu.2021.631954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242247PMC
June 2021

Dietary patterns and sarcopenia in a Chinese population.

Asia Pac J Clin Nutr 2021 Jun;30(2):245-252

Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China. Email:

Background And Objectives: Malnutrition is implicated as a key modifiable risk factor for sarcopenia. As such, a dietary pattern analysis, rather than an analysis of single food items or nutrients, may provide insights into the comprehensive contribution of diet and nutrition to the risk of sarcopenia. Accordingly, the aim of this study was to evaluate the relationships between main dietary patterns and sarcopenia.

Methods And Study Design: A total of 591 participants aged over 40 years were included in this cross-sectional study. A validated food-frequency questionnaire was used to assess their dietary intake, and principal component analysis (PCA) was used to identify the main dietary patterns. A multivariate logistic regression model was used to explore the associations between their main dietary patterns and the risk of sarcopenia.

Results: This study identified 56 cases of sarcopenia, equating to an overall detection rate of 9.48%. The PCA revealed four major dietary patterns among the participants: "coarse cereals and vegetables"; "beverages and animal organs"; "poultry, fish and shrimp"; and "fruits and pasta". After adjusting for age, sex, physical activity and smoking, individuals with the "coarse cereals and vegetables" dietary pattern had a 63.0% reduction in the risk of sarcopenia.

Conclusions: The "coarse cereals and vegetables" dietary pattern is negatively correlated with sarcopenia, and may reduce the risk of sarcopenia.
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http://dx.doi.org/10.6133/apjcn.202106_30(2).0009DOI Listing
June 2021

Prognostic Significance of Serum PD-L1 Level in Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma Treated with Combination Cytotoxic Chemotherapy.

Cancer Manag Res 2021 21;13:4935-4946. Epub 2021 Jun 21.

Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China.

Background: There are no useful biomarkers for the clinical outcome of advanced esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the prognostic value of soluble PD-L1 (sPD-L1) in serum of patients with locally advanced or metastatic ESCC who received cytotoxic chemotherapy as first-line treatment.

Materials And Methods: This study evaluated the expression pattern of PD-L1 by immunohistochemistry and sPD-L1 concentration, and correlation with clinicopathological factors and overall survival (OS) in 190 patients with ESCC.

Results: sPD-L1 concentration was highly expressed in ESCC, especially in female patients. Patients with a high sPD-L1 level (≥0.63 ng/mL) had a shorter OS than those with a low sPD-L1 level (<0.63 ng/mL). In a multivariate analysis, high sPD-L1 concentration remained an independent prognostic factor of OS after adjustment for possible confounders. However, tissue PD-L1 expression level was non-prognostic in this study.

Conclusion: There was no significant correlation between serum sPD-L1 concentration and tissue PD-L1 expression level. sPD-L1 concentration before treatment could be an effective and convenient biomarker of prognosis in patients with locally advanced or metastatic ESCC treated with combination cytotoxic chemotherapy.
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http://dx.doi.org/10.2147/CMAR.S312690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232859PMC
June 2021

The protective effect of small peptides from Periplaneta americana on hydrogen peroxide-induced apoptosis of granular cells.

In Vitro Cell Dev Biol Anim 2021 Jun 21. Epub 2021 Jun 21.

School of Public Health, Dali University, Dali, Yunnan Province, 671000, People's Republic of China.

This study investigates the protective effect of small peptides from Periplaneta americana (SPPA) on hydrogen peroxide (HO)-induced apoptosis of ovarian granular cells. HO was applied to human ovarian granular cells (KGN cell strains). Cell viability was tested by cell counting Kit-8 (CCK-8). Cell apoptosis was tested by flow cytometry, and a cell apoptosis model was established. The model cells were treated with SPPA, and the cell survival rate was monitored using the CCK-8 method. The oxidative stress state of cells was examined using SOD, ROS, MDA, and NO kits. The protein expression levels of SIRT1, p53, and the apoptosis-related gene Caspase3 were measured using Western Blot methodology. Relative to the control group, cell viability declined significantly after the HO treatment only (P < 0.01), while the apoptosis rate increased significantly (P < 0.01). The activity of SOD was weakened significantly (P < 0.01), while the cell levels of ROS, MDA, and NO increased dramatically (P < 0.01). Cell viability dramatically recovered (P < 0.01), and the SOD activity is hugely increased (P < 0.01) after SPPA treatment. In contrast, contents of ROS, MDA, and NO decreased sharply (P < 0.01), and significant dose-response relationships are characterized. Moreover, the HO treatment group showed significantly downregulated expression of SIRT1 (P < 0.01) but significantly upregulated expressions of p53 and Caspase3 (P < 0.01) compared to the control group. Following the SPPA treatment of apoptosis cells, expression of SIRT1 increased significantly, while expressions of p53 and Caspase3 declined significantly (P < 0.01). This study suggests that SPPA inhibits HO-induced human KGN cell apoptosis through antioxidation, and the SIRT1/p53 signal pathway mediates the antioxidation.
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http://dx.doi.org/10.1007/s11626-021-00586-2DOI Listing
June 2021

Low- and intermediate-risk myelodysplastic syndrome with pure red cell aplasia.

Hematology 2021 Dec;26(1):444-446

Department of Hematology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.

Objectives: Our aim is to investigate the clinical characteristics of low- and intermediate-risk myelodysplastic syndrome (MDS) with pure red cell aplasia (PRCA).

Methods: We retrospectively reviewed the patients of low- and intermediate-risk MDS patients who had been diagnosed with PRCA in our hospital between January 2010 and December 2019.

Results: There were 6 low- and intermediate-risk MDS patients with PRCA in our study, 1 male and 5 females, with a median age of 63.5 (50-75) years. It accounted for 7.7% (6/78) of all diagnosed PRCA cases and 1.67% (6/359) of diagnosed MDS cases during the same period. All patients were treated with multiple drugs, including recombinant human erythropoietin, cyclosporine, glucocorticoids, androgen, sirolimus, intravenous immunoglobulin and decitabine. Two patients achieved complete remission, two patients achieved partial remission and became blood transfusion independent. Two patients had no response and one patient died.

Conclusion: Low- and intermediate-risk MDS with PRCA was difficult to treat, but the prognosis was good.
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http://dx.doi.org/10.1080/16078454.2021.1929694DOI Listing
December 2021

Treatment and outcome patterns of patients with Waldenström's macroglobulinemia: a large, multicenter retrospective review in China.

Leuk Lymphoma 2021 Jun 9:1-8. Epub 2021 Jun 9.

Department of Hematology, Hubei, China.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 10/L, serum albumin <3.5 g/dl, β2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and β2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 10/L indicate a poor prognosis for patients with WM.
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http://dx.doi.org/10.1080/10428194.2021.1938030DOI Listing
June 2021

Malignant plasmacytes in bone marrow detected by flow cytometry as a predictor for the risk stratification system of multiple myeloma.

Cytometry B Clin Cytom 2021 May 31. Epub 2021 May 31.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.

Background: Multiple myeloma (MM) is a clonal disorder characterized by the proliferation of plasma cells and their accumulation within the bone marrow (BM). The flow cytometric analysis is an essential method for the hematological diseases because of high sensitivity.

Aims: This study evaluates the indication role of malignant plasmacytes (PCs) in BM detected by flow cytometry for the risk stratification of MM.

Methods: Whole BM samples from 92 newly diagnosed MM patients were included in the study. We collected 10 cells each sample by flow cytometry. Then we analyzed the correlation between the malignant PCs in BM and the characteristics of patients.

Results: In this study, patients were stratified according to different baseline characteristics and the median ratio of the malignant PCs were compared. The significant statistical differences (p < 0.05) were: Hb < 100 g/L versus ≥100 g/L; β2-microglobulin <3.5 mg/dL versus 3.5-5.5 mg/dL versus >5.5 mg/dL; LDH > 250 U/L versus LDH 250 U/L; ISS I versus ISS II versus ISS III; R-ISS I versus II versus III. The detailed data are showed in Table 2. The significant correlations were observed between the malignant PCs in BM and (Figure 1): plasma cell of biopsy, hemoglobin, β2-microglobulin, lactate dehydrogenase (LDH), creatinine. "Double hit" or "triple hit" are defined as containing any two or three of the high risk cytogenetic abnormalities (t(4;14), t(14;16), t(14;20); del17q; TP53 mutation; 1q21 gain) by mSMAR. "Double or triple hit" had independently unfavorable significance for overall survival. As expected, the malignant PCs of "double or triple hit" group is significantly higher than the group B (one high risk genetic factor) and the group A (normal cytogenetic) (p < 0.0001 and p < 0.019).

Conclusion: Multiparametric flow cytometry is a highly sensitive method to identify and quantify malignant PCs. And the ratio of malignant PCs detected by MFC showed strongly correlation with the severity of the pathology of MM. Malignant PCs in BM detected by flow cytometry could be regarded as a predictor for the risk stratification system of MM. Thus, it should be considered applying in the routine evaluation of MM at diagnosis and after therapy.
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http://dx.doi.org/10.1002/cyto.b.22024DOI Listing
May 2021

Enhanced tyrosine hydroxylase activity induces oxidative stress, causes accumulation of autotoxic catecholamine metabolites, and augments amphetamine effects in vivo.

J Neurochem 2021 May 15. Epub 2021 May 15.

Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

In Parkinson's disease, dopamine-containing nigrostriatal neurons undergo profound degeneration. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis. TH increases in vitro formation of reactive oxygen species, and previous animal studies have reported links between cytosolic dopamine build-up and oxidative stress. To examine effects of increased TH activity in catecholaminergic neurons in vivo, we generated TH-over-expressing mice (TH-HI) using a BAC-transgenic approach that results in over-expression of TH with endogenous patterns of expression. The transgenic mice were characterized by western blot, qPCR, and immunohistochemistry. Tissue contents of dopamine, its metabolites, and markers of oxidative stress were evaluated. TH-HI mice had a 3-fold increase in total and phosphorylated TH levels and an increased rate of dopamine synthesis. Coincident with elevated dopamine turnover, TH-HI mice showed increased striatal production of H O and reduced glutathione levels. In addition, TH-HI mice had elevated striatal levels of the neurotoxic dopamine metabolites 3,4-dihydroxyphenylacetaldehyde and 5-S-cysteinyl-dopamine and were more susceptible than wild-type mice to the effects of amphetamine and methamphetamine. These results demonstrate that increased TH alone is sufficient to produce oxidative stress in vivo, build up autotoxic dopamine metabolites, and augment toxicity.
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http://dx.doi.org/10.1111/jnc.15432DOI Listing
May 2021

Influence of calcination temperature on the fluorescence and magnetic properties of GdO:Tb, K nanoparticles.

Appl Opt 2021 Apr;60(12):3302-3307

: nanoparticles were synthesized by using diethylene glycol as a solvent and doped with 3 mol% ions. :, nanoparticles were calcinated at 600°C, 700°C, 800°C, and 900°C and subjected to the analysis of x-ray diffractometer, transmission electron microscope, Fourier transform infrared spectrometer, fluorescence spectroscopy, and magnetization. The experimental results showed that as the calcination temperature increased from 600°C to 800°C, the morphology and particle size of the :, nanoparticles did not change significantly; whereas when the calcination temperature rose from 800°C to 900°C, the structure of particles changed from cubic to monoclinic. As the temperature increased (below 800°C), the crystallinity of the cubic particles increased and the surface defects of the particles decreased, resulting in an increase in fluorescence intensity. For the monoclinic particles, the fluorescence intensity was significantly decreased and the magnetization was increased. The measured magnetic results confirmed the good paramagnetism of the synthesized nanoparticles.
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http://dx.doi.org/10.1364/AO.418490DOI Listing
April 2021

Complement C3a activates osteoclasts by regulating the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.

Cancer Biol Med 2021 May 7. Epub 2021 May 7.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, China.

Objective: Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease. However, the mechanism of C3a/C4a in osteoclasts MM patients remains unclear.

Methods: The formation and function of osteoclasts were analyzed after adding C3a/C4a . RNA-seq analysis was used to screen the potential pathways affecting osteoclasts, and the results were verified by Western blot, qRT-PCR, and pathway inhibitors.

Results: The osteoclast area per view induced by 1 μg/mL (mean ± SD: 50.828 ± 12.984%) and 10 μg/mL (53.663 ± 12.685%) of C3a was significantly increased compared to the control group (0 μg/mL) (34.635 ± 8.916%) ( < 0.001 and < 0.001, respectively). The relative mRNA expressions of genes, OSCAR/TRAP/RANKL/cathepsin K, induced by 1 μg/mL (median: 5.041, 3.726, 1.638, and 4.752, respectively) and 10 μg/mL (median: 5.140, 3.702, 2.250, and 5.172, respectively) of C3a was significantly increased compared to the control group (median: 3.137, 2.004, 0.573, and 2.257, respectively) (1 μg/mL = 0.001, = 0.003, < 0.001, and = 0.008, respectively; 10 μg/mL: < 0.001, = 0.019, < 0.001, and = 0.002, respectively). The absorption areas of the osteoclast resorption pits per view induced by 1 μg/mL (mean ± SD: 51.464 ± 11.983%) and 10 μg/mL (50.219 ± 12.067%) of C3a was also significantly increased (33.845 ± 8.331%) ( < 0.001 and < 0.001, respectively) compared to the control. There was no difference between the C4a and control groups. RNA-seq analysis showed that C3a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase (PI3K) signaling pathway. The relative expressions of PIK3CA/phosphoinositide dependent kinase-1 (PDK1)/serum and glucocorticoid inducible protein kinases (SGK3) genes and PI3K/PDK1/p-SGK3 protein in the C3a group were significantly higher than in the control group. The activation role of C3a in osteoclasts of MM patients was reduced by the SGK inhibitor (EMD638683).

Conclusions: C3a activated osteoclasts by regulating the PI3K/PDK1/SGK3 pathways in MM patients, which was reduced using a SGK inhibitor. Overall, our results identified potential therapeutic targets and strategies for MBD patients.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0430DOI Listing
May 2021

Comparison between preoperative two-dimensional shear wave elastography and indocyanine green clearance test for prediction of post-hepatectomy liver failure.

Quant Imaging Med Surg 2021 May;11(5):1692-1700

Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu, China.

Background: Post-hepatectomy liver failure (PHLF) is one of the most serious complications and major causes of liver resection mortality. The purpose of this study is to investigate and compare the performance of preoperative two-dimensional shear wave elastography (2D-SWE) and the indocyanine green (ICG) clearance test for the prediction of PHLF.

Methods: A total of 172 consecutive patients who were undergoing major liver resection were prospectively identified. Patients were evaluated by preoperative 2D-SWE and ICG clearance test. According to the International Study Group of Liver Surgery (ISGLS) recommendations, No PHLF, PHLF A, PHLF B, and PHLF C group classifications were defined. The differences in liver stiffness value (LSV) and ICG retention rate at 15 minutes (ICGR15) among the different PHLF classifications were investigated. The performance of LSV and ICGR15 for diagnosing different classifications of PHLF was compared.

Results: PHLF occurred in 43 (25.0%) patients, and 24 (14.0%) patients were grade A, 14 (8.1%) were grade B, and 5 (2.9%) were grade C. Both LSV and ICGR15 of the PHLF C group were significantly higher than those of the No PHLF group (P=0.025, P=0.001, respectively). According to univariate and multivariate logistic regression analysis, LSV and ICGR15 were significantly related to PHLF (P=0.051, P=0.084, respectively). For diagnosis of ≥ PHLF A, ≥ PHLF B, and ≥ PHLF C, the areas under the receiver operating characteristic curve (AUCs) for 2D-SWE were 0.624 [95% confidence interval (CI): 0.536-0.712, P=0.015], 0.699 (95% CI: 0.576-0.821, P=0.005), and 0.831 (95% CI: 0.737-0.925, P=0.01), respectively. The AUCs of the ICG clearance test were 0.631 (95% CI: 0.542-0.721, P=0.01), 0.570 (95% CI: 0.436-0.704, P=0.32), and 0.717 (95% CI: 0.515-0.920, P=0.098), respectively. The AUC of LSV for the diagnosis of ≥ PHLF A was comparable to that of ICGR15 (P=0.17). The AUCs of LSV were significantly higher than those of ICGR15 for the diagnosis of ≥ PHLF B (P=0.002) and C (P=0.038).

Conclusions: 2D-SWE demonstrates the potential to aid in the prediction of the severity of PHLF. Our findings also suggest that the performance of 2D-SWE is better than the ICG clearance test.
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http://dx.doi.org/10.21037/qims-20-640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047360PMC
May 2021

Efficacy, tolerability, patient usability, and satisfaction with a 2 mL pre-filled syringe containing secukinumab 300 mg in patients with moderate to severe plaque psoriasis: results from the phase 3 randomized, double-blind, placebo-controlled ALLURE study.

J Dermatolog Treat 2021 Apr 26:1-9. Epub 2021 Apr 26.

Novartis Pharma AG, Basel, Switzerland.

Background: Evidence shows good tolerability in patients for subcutaneous injection volumes up to 3 mL.

Objectives: We investigated efficacy, pharmacokinetics, and tolerability of secukinumab 300 mg/2 mL pre-filled syringe (PFS) in patients with moderate to severe plaque psoriasis.

Methods: ALLURE was a 52-week, multicenter, randomized (1:1:1), double-blind, placebo-controlled, parallel-group study. Co-primary endpoints were secukinumab Psoriasis Area Severity Index (PASI) 75 and Investigator's Global Assessment modified 2011 0/1 (IGA mod 2011 0 or 1) responses at week 12 versus placebo. Other endpoints included the Self-Injection Assessment Questionnaire (SIAQ), and the ability to follow the instructions for use (IFU).

Results: Overall, 214 patients were randomized. The secukinumab 300 mg/2 mL PFS showed superiority over placebo for both PASI 75 (88.9% versus 1.7%; <.0001) and IGA mod 2011 0 or 1 (76.4% versus 1.4%; <.0001) responses at week 12. All secondary efficacy endpoints were met. The SIAQ scores were similar across groups and improved similarly over 12 weeks. All patients completed critical steps in the IFU at week 1.

Conclusions: The secukinumab 300 mg/2 mL PFS groups showed superiority versus placebo, and it was a safe, effective, and convenient option for patients with psoriasis. NCT02748863.
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http://dx.doi.org/10.1080/09546634.2021.1902925DOI Listing
April 2021

Exercise Ameliorates Fluoride-induced Anxiety- and Depression-like Behavior in Mice: Role of GABA.

Biol Trace Elem Res 2021 Apr 6. Epub 2021 Apr 6.

College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, 030801, Shanxi, China.

Fluoride exposure caused anxiety- and depression-like behavior in mice. Meanwhile, exercise contributes to relieve anxiety and depression. However, the effects of exercise on anxiety- and depression-like behavior in fluorosis mice remain unclear. In the current study, thirty-six Institute of Cancer Research (ICR) female mice were randomly assigned to four groups: control group (C, gavage with distilled water); exercise group (E, gavage with distilled water and treadmill exercise (speed, 10 m/min; time, 30 min/day)); fluoride group (F, gavage with 24 mg/kg sodium fluoride (NaF)); and exercise plus fluoride group (EF, gavage with 24 mg/kg NaF and treadmill exercise). All treatments lasted for 8 weeks. A number of entries into and time spent in the open zone in the elevated zero maze (EZM), resting time in the tail suspension test (TST) and levels of serotonin (5-HT) and gamma-aminobutyric acid (GABA), were significantly altered in F when compared to C. Meanwhile, the anxiety-like behavior in the EZM and the depression-like behavior in the TST were significantly improved in EF when compared to group F. Exercise significantly enhanced fluoride-induced low GABA level, with less effect on the concentration of 5-HT. Moreover, the mRNA and protein expressions of GABA synthesis and transport-related proteins of glutamic acid decarboxylase (GAD) 65 and GAD67 and vesicular GABA transporter (VGAT) were all strikingly decreased in F, while those in EF were increased. In conclusion, exercise ameliorates anxiety- and depression-like behavior in fluorosis mice through increasing the expressions of GABA synthesis and transport-related proteins, rather than 5-HT system.
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http://dx.doi.org/10.1007/s12011-021-02678-2DOI Listing
April 2021

Exercise Ameliorates Fluoride-induced Anxiety- and Depression-like Behavior in Mice: Role of GABA.

Biol Trace Elem Res 2021 Apr 6. Epub 2021 Apr 6.

College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, 030801, Shanxi, China.

Fluoride exposure caused anxiety- and depression-like behavior in mice. Meanwhile, exercise contributes to relieve anxiety and depression. However, the effects of exercise on anxiety- and depression-like behavior in fluorosis mice remain unclear. In the current study, thirty-six Institute of Cancer Research (ICR) female mice were randomly assigned to four groups: control group (C, gavage with distilled water); exercise group (E, gavage with distilled water and treadmill exercise (speed, 10 m/min; time, 30 min/day)); fluoride group (F, gavage with 24 mg/kg sodium fluoride (NaF)); and exercise plus fluoride group (EF, gavage with 24 mg/kg NaF and treadmill exercise). All treatments lasted for 8 weeks. A number of entries into and time spent in the open zone in the elevated zero maze (EZM), resting time in the tail suspension test (TST) and levels of serotonin (5-HT) and gamma-aminobutyric acid (GABA), were significantly altered in F when compared to C. Meanwhile, the anxiety-like behavior in the EZM and the depression-like behavior in the TST were significantly improved in EF when compared to group F. Exercise significantly enhanced fluoride-induced low GABA level, with less effect on the concentration of 5-HT. Moreover, the mRNA and protein expressions of GABA synthesis and transport-related proteins of glutamic acid decarboxylase (GAD) 65 and GAD67 and vesicular GABA transporter (VGAT) were all strikingly decreased in F, while those in EF were increased. In conclusion, exercise ameliorates anxiety- and depression-like behavior in fluorosis mice through increasing the expressions of GABA synthesis and transport-related proteins, rather than 5-HT system.
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http://dx.doi.org/10.1007/s12011-021-02678-2DOI Listing
April 2021

Comparison of preoperative two-dimensional shear wave elastography, indocyanine green clearance test and biomarkers for post hepatectomy liver failure prediction in patients with hepatocellular carcinoma.

BMC Gastroenterol 2021 Mar 31;21(1):142. Epub 2021 Mar 31.

Department of Ultrasound, West China Hospital of Sichuan University, No. 37, Guoxue Xiang, Chengdu, 610041, Sichuan, China.

Background: The preoperative prediction of post hepatectomy liver failure (PHLF) is essential, but there is no gold standard for the prediction at present, and the efficacy of different methods for the prediction has not been compared systematically. In this study, we aimed to compare the efficacy of preoperative two-dimensional shear wave elastography (2D-SWE), indocyanine green (ICG) clearance test and biomarkers for PHLF prediction in patients with hepatocellular carcinoma (HCC).

Methods: We retrospectively studied 215 patients with HCC, who had undergone major liver resection in our hospital. Preoperative data of each patient, including liver stiffness value (LSV) of underlying hepatic parenchyma measured by 2D-SWE, ICG retention rate at 15 min (ICG-R15) measured by ICG clearance test, albumin-bilirubin (ALBI) scores, aspartate aminotransferase-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) were collected for analysis. Post hepatectomy outcomes of study patients were also recorded for assessment of PHLF. The study patients were divided into development cohort (133 patients without PHLF, and 17 patients with PHLF) and validation cohort (59 patients without PHLF, and 6 patients with PHLF) randomly.

Results: In the development cohort, LSV, ICG-R15 and ALBI scores were significantly different between patients with and without PHLF, while no significant difference of APRI and FIB-4 scores was found. LSV had higher AUC (the area under the receiver operating characteristic curve) (AUC = 0.795) for PHLF prediction than ICG-R15 (AUC = 0.619) and ALBI scores (AUC = 0.686) (p < 0.05 for all comparisons). In the validation cohort, the cutoff value of LSV obtained from the development cohort, 10.35 kPa,  revealed higher specificity (76.3%) for PHLF prediction than ICG-R15 (specificity: 66.1%) and ALBI scores (specificity: 69.5%) (p < 0.0001).

Conclusions: Compared with ICG-R15, ALBI scores, APRI and FIB-4, LSV measured by 2D-SWE may demonstrate better efficacy for preoperative PHLF prediction in patients with HCC.
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http://dx.doi.org/10.1186/s12876-021-01727-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010946PMC
March 2021

Cyclin-dependent kinase inhibitor roscovitine attenuates liver inflammation and fibrosis by influencing initiating steps of liver injury.

Clin Sci (Lond) 2021 Apr;135(7):925-941

Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China.

Liver diseases present a significant public health burden worldwide. Although the mechanisms of liver diseases are complex, it is generally accepted that inflammation is commonly involved in the pathogenesis. Ongoing inflammatory responses exacerbate liver injury, or even result in fibrosis and cirrhosis. Here we report that roscovitine, a cyclin-dependent kinase (CDK) inhibitor, exerts beneficial effects on acute and chronic liver inflammation as well as fibrosis. Animal models of lipopolysaccharide (LPS)/d-galactosamine- and acute or chronic CCl4-induced liver injury showed that roscovitine administration markedly attenuated liver injury, inflammation and histological damage in LPS/d-galactosamine- and CCl4-induced acute liver injury models, which is consistent with the results in vitro. RNA sequencing (RNA-seq) analysis showed that roscovitine treatment repressed the transcription of a broad set of pro-inflammatory genes involved in many aspects of inflammation, including cytokine production and immune cell proliferation and migration, and inhibited the TGF-β signaling pathway and the biological process of tissue remodeling. For further validation, the beneficial effect of roscovitine against inflammation was evaluated in chronic CCl4-challenged mice. The anti-inflammation effect of roscovitine was observed in this model, accompanied with reduced liver fibrosis. The anti-fibrotic mechanism involved inhibition of profibrotic genes and blocking of hepatic stellate cell (HSC) activation. Our data show that roscovitine administration protects against liver diseases through inhibition of macrophage inflammatory actions and HSC activation at the onset of liver injury.
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http://dx.doi.org/10.1042/CS20201111DOI Listing
April 2021

Expression and function of SLAMF6 in CD8 T lymphocytes of patients with severe aplastic anemia.

Cell Immunol 2021 Jun 15;364:104343. Epub 2021 Mar 15.

Department of Hematology, Tianjin Medical University General Hospital, 154 Anshan Street, Heping District, Tianjin 300052, PR China. Electronic address:

This study investigated the expression status of signaling lymphocytic activation molecule family 6 (SLAMF6) in CD8 T lymphocytes of patients with severe aplastic anemia (SAA) and its association with the clinical indicators and immune status of the disease. The effects of SLAMF6 on the function and apoptosis of CD8 T lymphocytes were also investigated. Levels of SLAMF6 and SLAM-associated protein in the CD8 T lymphocytes of SAA patients were significantly lower than the normal controls, and they were positively correlated with hematopoietic-related indicators but negatively correlated with the levels of functional molecules of CD8 T lymphocytes. After blocking SLAMF6, CD8 T lymphocyte functional molecule secretion was upregulated and RICD was downregulated in SAA patients, suggesting that SLAMF6, is involved in the pathogenetic mechanism of SAA by regulating CD8 T lymphocyte functional molecule secretion and RICD levels. SLAMF6 may be a novel target for the regulation of CD8 T lymphocyte homeostasis.
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http://dx.doi.org/10.1016/j.cellimm.2021.104343DOI Listing
June 2021

Effects of phosphorus application rates on spring rape yield and soil phosphorus balance.

Ying Yong Sheng Tai Xue Bao 2021 Mar;32(3):906-912

College of Natural Resource and Environment, Northwest A&F University, Yangling 712100, Shaanxi, China.

Excessive application of phosphorus fertilizer leads to high soil available phosphorus content but low phosphorus use efficiency in the main production areas of spring rape in eastern Qinghai. Understanding the effects of phosphorous application rates on the growth, phosphorus absorption, soil phosphorus balance in the field of spring rape could improve nutrient management of spring rape, and benefit for the sustainable development of agriculture in Qinghai-Tibet Plateau. A field experiment was carried out in Huzhu County of Qinghai Province from 2017 to 2018. We mea-sured seed yield, phosphorus uptake and oil content of spring rape under five phosphorous fertilizer rates (0, 30, 60, 90 and 120 kg PO·hm). In 2017, the seed yield and oil production of spring rape with the rate of 60 kg·hm were significantly higher than that of no phosphorus fertilizer treatment. In contrast, seed yield and oil production did not increase when the phosphorus rate exceeded 60 kg·hm in 2017. Phosphorus rate did not affect seed yield, phosphorus accumulation, and oil production of spring rape in 2018. The phosphorus use efficiency was low in both years, with a mean value of 6.7%. Phosphorus fertilizer application caused phosphorus surplus in soils, which was low when the application rate was less than 60 kg·hm. Our results suggest that the rate of 60 kg·hm is suitable for spring rape production in the eastern Qinghai Province.
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http://dx.doi.org/10.13287/j.1001-9332.202103.010DOI Listing
March 2021

Upregulated expression of leukocyte immunoglobulin-like receptor A3 in patients with severe aplastic anemia.

Exp Ther Med 2021 Apr 11;21(4):346. Epub 2021 Feb 11.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Severe aplastic anemia (SAA) is a rare and potentially life-threatening disease characterized by pancytopenia and bone marrow (BM) hypoplasia. In a previous study by our group, increased expression of leukocyte immunoglobulin-like receptors A (LILRA), LILRA3 in myeloid dendritic cells (mDCs) and LILRA5 in CD34 cells in SAA was detected using proteomics techniques, highlighting their potential role in disease pathogenesis. In the present study, the expression of LILRA1-6 mRNA was assessed in the BM mononuclear cells of patients with SAA using reverse transcription-quantitative (RT-q)PCR. The expression of homogenic LILRA3 and LILRA5 isoform on mDCs, as well as CD34, CD3CD8, CD19 and CD14 cells, was detected using flow cytometry. mDCs were then induced, cultured and sorted. The expression of LILRA3 was confirmed using RT-qPCR and western blot analyses. The serum levels of soluble LILRA3 were measured using ELISA. Furthermore, the relationship between LILRA3 expression and disease severity was assessed. The results indicated increased LILRA3 mRNA expression in patients with SAA. The percentage of LILRA3 in BM mDCs and CD34 cells was increased. Compared with controls, the relative LILRA3 mRNA expression and the relative protein intensity were highly increased in SAA mDCs. The serum LILRA3 levels in patients with SAA were also increased. The proportion of LILRA3CD11C human leukocyte antigen (HLA)-DR/CD11CHLA-DR cells was positively correlated with the ratio of LILRA3CD34/CD34 cells and the expression of LILRA3 mRNA. Taken together, the expression of LILRA3 on mDCs of patients with SAA was increased, which may affect the function of mDCs. LILRA3 may have a significant role in the immune pathogenesis of SAA.
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http://dx.doi.org/10.3892/etm.2021.9777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903422PMC
April 2021

Long Non-coding RNA MALAT1 Contributed to the Proliferation of PNH Clone in Paroxysmal Nocturnal Hemoglobinuria Patients.

Turk J Haematol 2021 Mar 17. Epub 2021 Mar 17.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.

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http://dx.doi.org/10.4274/tjh.galenos.2021.2021.0065DOI Listing
March 2021

Current research status of HLA in immune-related diseases.

Immun Inflamm Dis 2021 Jun 3;9(2):340-350. Epub 2021 Mar 3.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, PR China.

Human leukocyte antigen (HLA), also known as human major histocompatibility complex (MHC), is encoded by the HLA gene complex, and is currently known to have the highest gene density and the most polymorphisms among human chromosomal areas. HLA is divided into class I antigens, class II antigens, and class III antigens according to distribution and function. Classical HLA class I antigens include HLA-A, HLA-B, and HLA-C; HLA class II antigens include HLA-DP, HLA-DQ, and HLA-DR; nonclassical HLA class I and II molecules include HLA-F, E, H, X, DN, DO, and DM; and others, such as complement, are class III antigens. HLA is closely related to the body's immune response, regulation, and surveillance and is of great significance in the study of autoimmune diseases, tumor immunity, organ transplantation, and reproductive immunity. HLA is an important research topic that bridges immunology and clinical diseases. With the development of research methods and technologies, there will be more discoveries and broader prospects.
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http://dx.doi.org/10.1002/iid3.416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127548PMC
June 2021

Fluorine-Induced Surface Metallization for Ammonia Synthesis under Photoexcitation up to 1550 nm.

Angew Chem Int Ed Engl 2021 May 9;60(20):11173-11179. Epub 2021 Apr 9.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, 130012, P. R. China.

The first observation of surface metallization of TiO induced by fluoride ions is presented. The emerging metallic states are contributed by the 3d orbital of surface Ti and the 2p orbital of surface bridging F, which are intrinsically originated from the strong electron repulsion between F and adjacent Ti . The metalized TiO with reduced work function and downward band bending possesses high electron-donating power to supported Ru species via atomic-scale ohmic contacts, exhibiting unprecedented photocatalytic performances for ammonia synthesis across the entire solar spectrum region (200-1550 nm) at room temperature. Mechanism and kinetic analysis revealed that the loaded Ru could behave as efficient electron sinks to accumulate photogenerated electrons and that the metallic surface markedly enhanced the dissociation of H and N by the hot electrons generated by the visible or even infrared light irradiation.
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http://dx.doi.org/10.1002/anie.202100572DOI Listing
May 2021

Tribological Behavior of Phenolic Resin-Based Friction Composites Filled with Graphite.

Materials (Basel) 2021 Feb 5;14(4). Epub 2021 Feb 5.

School of Materials Science and Engineering, Dalian Jiaotong University, Dalian 116028, China.

In this paper, the influence of graphite (Gr) on the dry sliding tribological properties of phenolic resin (PF) composites was studied under different sliding speeds of 3.1-47.1 m/s. The wear mechanism was investigated by the observation of the morphology of the transfer layer during the dry sliding process. It was found that the addition of Gr could decrease the friction coefficient and wear rate effectively, and the friction coefficient and wear rate decreased with the increase of Gr content in the range of 10-30 vol.%. The dominant wear mechanisms of PF-based friction composites changed from adhesive wear to fatigue wear (in the form of peeling-off) in the high sliding speed condition after the addition of Gr. The addition of Gr effectively reduced the sensitivity of PF-based friction materials to sliding speeds, and thus enhanced the stability of the friction coefficient. When the content of Gr was above 20 vol.%, the stability of the friction coefficient was relatively steady.
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http://dx.doi.org/10.3390/ma14040742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914663PMC
February 2021

The role of Pim kinase in immunomodulation.

Am J Cancer Res 2020 1;10(12):4085-4097. Epub 2020 Dec 1.

Department of Hematology, Tianjin Medical University General Hospital Tianjin 300052, P. R. China.

Pim kinase, which has three isozymes (Pim-1, Pim-2 and Pim-3), is a serine/threonine kinase abnormally expressed in many cancers. High Pim kinase expression has been recognized to be associated with disease progression and prognosis. It is well accepted that Pim kinase is considered a clinical biomarker and potential therapeutic target for tumor cell. In recent years, researches verified the role of Pim kinase in immunomodulation. The mechanisms by which Pim kinase modulates the immune microenvironment and regulates immune cells, as well as the effects of Pim kinase inhibitors on immunity, have not been systematically described. This review comprehensively focuses on the current research status of Pim kinase pathways and the immune regulation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783746PMC
December 2020

Study on Tim3 Regulation of Multiple Myeloma Cell Proliferation NF-κB Signal Pathways.

Front Oncol 2020 19;10:584530. Epub 2020 Nov 19.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.

Objective: As an important negative regulatory factor of immunological cells, Tim3 plays a regulating role in tumor immune microenvironment. The purpose of this study was to investigate the expression of Tim3 on MM cells and its effect on the proliferation and apoptosis of MM cells, as well as its potential mechanism.

Methods: In this study, the expression of Tim3 was detected on myeloma cells (CD38CD138 cells) of bone marrow by flow cytometry (FCM) from 167 patients with MM and 51 healthy donors as controls and making correlation analysis with related clinical indexes. , MM cell lines (RPMI-8226 and U266) were treated with Tim3 knock-down alone, bortezomib alone and combination of Tim3 knock-down and bortezomib, then cell proliferation, cell apoptosis and downstream signaling pathway were detected by CCK-8, FCM, RT-PCR and western blot.

Results: The expression of Tim3 on myeloma cells in MM patients was significantly higher than normal control group and positively correlated with β microglobulin, creatine, and plasma cells of bone marrow, negatively correlated with hemoglobin and red blood cells. , we validated the high expression of Tim3 in RPMI-8226 and U266 cell lines. After Tim3 knock-down, the cell proliferation was inhibited and cell apoptosis was induced, the relative mRNA and protein expression of Tim3 and NF-κB signal pathway (PI3K, AKT, mTOR, NF-κB) were significantly decreased. Also, the cell proliferation was inhibited, cell apoptosis was increased, the relative mRNA and protein expression of NF-κB were decreased significantly in combination group than bortezomib or Tim3 knock-down group.

Conclusions: The high expression of Tim3 on MM cells is associated with progression of MM patients. Tim3 maybe regulate the proliferation of MM cells NF-κB signal pathway. Down-regulation of Tim3 expression can inhibit proliferation and induce apoptosis of MM cells, also has an additive inhibitory effect of bortezomib on NF-κB signaling pathway, then inhibit proliferation and induce apoptosis. Therefore, Tim3 may be a potential target for the treatment of MM.
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http://dx.doi.org/10.3389/fonc.2020.584530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710973PMC
November 2020

Safety and Efficacy of Eltrombopag and Romiplostim in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis.

Front Oncol 2020 26;10:582686. Epub 2020 Nov 26.

Hematology Department of Tianjin, Medical University General Hospital, Tianjin, China.

Background And Aim: Many studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS.

Methods: A full-scale search strategy was used to search relevant published studies in PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library until January 2020 using a random-effects model and the pooled risk ratio (RR) with 95% confidence interval as the effect indicator. Statistical analyses were performed using RevMan 5.3.

Results: This meta-analysis included eight studies comprising 1047 patients. A lower RR of overall response rate (ORR) (RR: 0.65; 95% CI, 0.47-0.9) and grade ≥3 bleeding events (RR: 0.36; 95% CI, 0.36-0.92) were observed after romiplostim and eltrombopag treatment compared with placebo. The pooled RR for the ORR and grade ≥3 bleeding events were 0.58 (95% CI: 0.41-0.83, P = 0.003) and 0.6 (95% CI: 0.37-0.96, P = 0.03) in eltrombopag, respectively. A lower ORR in intermediate- or high-risk MDS (RR: 0.63; 95% CI: 0.45-0.88, P = 0.006) was observed. No difference in mortality, serious adverse events, platelet transfusion, hematologic improvement, and AML transformation was observed.

Conclusions: Thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag were effective in reducing bleeding events, especially grade ≥3 bleeding events. However, it might reduce the ORR of MDS, especially in eltrombopag treatment group or high-risk MDS group. Due to the limited treatment of MDS and the poor response to the drug, this may be a selection method for MDS combined with fatal bleeding, although further research is needed to confirm the effectiveness of this approach.
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http://dx.doi.org/10.3389/fonc.2020.582686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727449PMC
November 2020

The best of both worlds? The economic effects of a hybrid fee-for-service and prospective payment reimbursement system.

Health Econ 2021 Mar 14;30(3):505-524. Epub 2020 Dec 14.

School of Political Science and Economics, Waseda University, Tokyo, Japan.

Countries seeking to move away from a purely fee-for-service (FFS) system may consider a hybrid approach whereby only some procedures are paid by FFS while others are paid prospectively. Yet little evidence exists whether such a hybrid payment system contains overall costs without adverse influences on health outcomes. In 2003, Japan experienced a reform from FFS to a hybrid payment system in which only some inpatient procedures were paid prospectively. We exploit this reform to test how such a hybrid system affects overall costs and health outcomes. Briefly, we find that healthcare providers responded opportunistically to the reform, moving some procedures out of the bundled inpatient setting to FFS services, leading to no reduction in cost. There was some evidence of a moderate deterioration in health outcomes, in terms of a decline in the probability of symptoms being cured at discharge. In sum, our results suggest that in some cases, a hybrid payment system can be non-superior to either FFS or prospective payment system.
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http://dx.doi.org/10.1002/hec.4205DOI Listing
March 2021