[Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience].

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.

Pravastatin alleviates oxidative stress and decreases placental trophoblastic cell apoptosis through IL-6/STAT3 signaling pathway in preeclampsia rats.

OBJECTIVE: The aim of this study was to explore the effects of pravastatin on oxidative stress and placental trophoblastic cell apoptosis in preeclampsia rats via the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway. MATERIALS AND METHODS: Experimental rats were randomly assigned into three groups, including control group (C group), model group (M group) and pravastatin group (P group). The rat model of preeclampsia was successfully established. Blood pressure, urinary protein and nitric oxide (NO) as well as oxidative stress indicators in rats were detected at 7, 14 and 21 d, respectively. The content of serum IL-6 was determined via enzyme-linked immunosorbent assay (ELISA). The messenger ribonucleic acid (mRNA) expression of IL-6 in the placenta of rats in each group was detected using quantitative polymerase chain reaction (qPCR). Western blotting (WB) was used to determine the protein expression level of STATs in the placental tissues of rats. In addition, cell counting kit (CCK)-8 assay was conducted to detect the proliferation of rat placental trophoblasts. RESULTS: The content of serum NO was (14.32±2.32) µM in M group, (28.37±3.32) µM in C group and (22.54±3.12) µM in P group, respectively. It was significantly elevated in P group compared with M group (p<0.05). Blood pressure in M group was evidently higher than that in C group at 14 and 21 d (p<0.05). However, P group exhibited distinctly lower blood pressure than M group (p<0.05). No statistically significant differences were observed in the urinary protein of rats among all the three groups at 7 d (p>0.05). At 14 and 21 d, the content of urinary protein in M group was considerably higher than that in C group (p<0.05). However, P group had distinctly lower urinary protein content than M group (p<0.05). Compared with C group, the content of malondialdehyde (MDA) and advanced oxidation protein products (AOPP) rose significantly in M group, whereas the content of superoxide dismutase (SOD) declined remarkably (p<0.05). In comparison with M group, P group exhibited declined MDA and AOPP content and increased SOD content, with statistically significant differences between the two groups (p<0.05). The expression level of serum IL-6 in rats in M group was markedly higher than that in C group (p<0.05). Meanwhile, the expression level of serum IL-6 evidently declined in P group compared with M group (p<0.05). Compared with C group, the protein expressions of phosphorylated STAT1 (p-STAT1) and p-STAT3 were considerably up-regulated in M group (p<0.01). However, they decreased prominently in P group in comparison with M group (p<0.01). C group exhibited a remarkably worse proliferation ability of rat placental trophoblasts than C group (p<0.01). In comparison with M group, the proliferation ability of rat placental trophoblasts was evidently enhanced in P group (p<0.05). Flow cytometry results indicated that the apoptosis of trophoblastic cells increased significantly in M group compared with that in C group (p<0.01). However, it significantly declined in P group in comparison with M group (p<0.05). CONCLUSIONS: Pravastatin can repress the IL-6/STAT3 signaling pathway to alleviate oxidative stress, improve preeclampsia and decrease the apoptosis of placental trophoblastic cells in preeclampsia rats.

[Different effects of pravastatin on sFlt-1, PlGF and VEGF in different preeclampsia-like mouse models].

Objective: To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)-like mouse models. Methods: C57BL/6J mice were randomly subcutaneously injected with N-nitro-L-arginine methyl ester (L-NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE-like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L-NAME+Pra, LPS+Pra, Con+Pra) and saline (L-NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt-1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real-time fluorescence quantitative PCR (RT-PCR). Results: (1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50±4.31) levels were significantly increased in L-NAME+Pra group compared with L-NAME+NS group (all P<0.05). Serum VEGF (202.30±4.90, 144.50±6.71) and PlGF (121.50±3.86, 95.41±4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt-1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt-1 level in L-NAME+Pra group was significantly lower than that in L-NAME+NS group (2.60±0.06, 583.70±9.83; all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66±0.14) in the liver of mice in the L-NAME+Pra group were significantly higher than those in the L-NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L-NAME+Pra group were not significantly different from those of L-NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT-PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L-NAME+Pra group were not significantly different from those in L-NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05). Conclusions: Pra has different regulatory effects on vascular endothelial function in different PE-like models. It reveals that different pathogenesis and pathways exist in different PE-like changes.

[Regulation of pravastatin on long-chain fatty acid oxidative enzyme in pre-eclampsia-like mouse model].

Objective: To investigate the modulation of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression by pravastatin in pre-eclampsia-like mouse model. Methods: C57BL/6J mice were randomly injected with N-nitro-L-arginine methyl ester (L-NAME) as pre-eclampsia-like model group (PE) or saline as normal pregnancy control group (Con) respectively, from gestational the 7th to 18th day. For each group, pravastatin (PE+Pra, Con+Pra group) or saline (PE+N, Con+N Group) was given from the 8th to 18th day of gestation, respectively. Liver and placenta of pregnant mice were collected on gestational day 18. The LCHAD protein expression and mRNA levels of liver and placenta were detected through western blot, immunohistochemistry and real-time quantitative PCR. Results: (1) The average arterial pressure of pregnant mice increased gradually from the 8th to 18th day in PE+N group, but decreased in PE+Pra group from gestational 10th day, 24 hour urinary protein levels in PE+N group [(1 494 ± 201) µg] were significantly higher than that in Con+N group [(935±128) µg, P<0.01], and also higher than that in PE+Pra group [(981±116) µg, P<0.01].(2) The results of western blot: the expression of LCHAD was significantly lower in PE+N group (liver: 0.64±0.11, placenta: 0.48±0.06) than that in Con+N group (liver: 1.06±0.10, placenta: 0.60±0.10), and lower than that in PE+Pra group (liver: 0.99±0.04, placenta: 0.60±0.08; all P<0.01).(3)The results of real-time quantitative PCR: the levels of LCHAD mRNA in liver and placenta in PE+N group (liver: 0.621±0.128, placenta: 0.646±0.129) were significantly decreased compared with Con+N group (liver: 1.007±0.130, placenta: 1.004±0.103; all P<0.01), but there was no significant difference between PE+Pra group (liver: 0.693±0.678, placenta: 0.662±0.183; P>0.05). (4) LCHAD protein was expressed widely and evenly in liver. The expression in placental cytotrophoblast and syncytial trophoblast cells located in outer layer of villous in labyrinth layer was the most. The expression of LCHAD was significantly lower in PE+N group (liver: 0.062±0.016, placenta: 0.147±0.018) than that in Con+N group (liver: 0.126±0.013, placenta: 0.183±0.024), and lower than that in PE+Pra group (liver: 0.111±0.017, placenta: 0.174±0.027; all P<0.05). Conclusion: Pravastatin could upregulate the LCHAD protein expression of liver and placenta in the pre-eclampsia-like mouse, which may be a mechanism to improve the clinical manifestations of pre-eclampsia.

[Clinical characteristics of bone disease in multiple myeloma and clinical significance of monitoring bone metabolic markers].

OBJECTIVE: To observe the clinical characteristics of bone disease in patients with multiple myeloma (MM) and the clinical significance of monitoring bone metabolic markers. METHODS: The data of 178 MM cases newly diagnosed in Beijing Ji Shui Tan Hospital from January 2009 to June 2014 were reviewed to analysis the types and classification of bone disease and to observe the clinical characteristics of patients with different grades of bone disease. The levels of bone metabolic markers total procollagen type Ⅰ N-terminal peptide (tPINP) and ß C-terminal telopeptide of type Ⅰ collagen (ß-CTX) were monitored regularly in the two years following treatment in 66 cases. RESULTS: (1) Among the 178 newly diagnosed MM cases, 167 cases complained of pain in bones on first visit, 35 cases combined with hypercalcemia, 83 cases combined with osteoporosis, 154 cases combined with osteolytic bone destruction, and 73 cases combined with pathologic fracture. The most common osteolytic location was the spine. The most common fracture sites was the spine. (2) According to bone disease grading, the 178 cases were divided into group A (bone grade 0-2, n=51) and group B(bone grade 3-4, n=127). There were no significant differences between group A and group B in gender, median age, therapeutic effect/ineffec, median overall survival, median progress-free survival, mean serum lactic dehydrogenase, mean albumin, urine light chains and serum creatinine(all P>0.05). Compared with group A, group B had lower hemoglobin level[(99.78±29.93)vs (108.84±29.30) g/L], and higher blood calcium level[(2.47±0.40)vs (2.30±0.29) mmol/L], serum ß2-microglobuin level[(6.04±4.84)vs (4.12±3.97)mg/L], and bone marrow plasma cells percentage(33.30%±24.87% vs 23.51%±22.67%)(all P<0.05). (3) Before treatment, the levels of ß-CTX and tPINP in patients of group B(n=47) were higher than those in group A(n=19)(median 0.78 vs 0.42 µg/L, 60.95 vs 43.47 µg/L, both P<0.05). The ratio of ß-CTX /tPINP in group B was higher than that in group A (median 0.017 vs 0.012, P<0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both group A and group B (both P>0.05), the level of ß-CTX decreased significantly compared with that before treatment in both groups(median 0.16 vs 0.42 µg/L, 0.26 vs 0.78 µg/L, both P<0.05); the ratio of ß-CTX /tPINP decreased significantly compared with that before treatment in both group A and in group B(median 0.008 vs 0.012, 0.011 vs 0.017, both P<0.05). There were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that after 3 months in both group A and group B (all P>0.05). (4)All patients were divided into two groups according to the therapeutic effect: effective group included patients who reach the effect of partial remission or better remission(n=48), while ineffective group included patients who did not reach the effect of partial remission(n=18). Before treatment there were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio between the effective groupand the ineffective group (all P>0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both effective group and ineffective group (all P>0.05), but the level of ß-CTX decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.24 vs 0.60 µg/L, 0.44 vs 0.95 µg/L, both P<0.05). The ratio of ß-CTX /tPINP decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.005 vs 0.012, 0.005 vs 0.011, both P<0.05). There were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that for 3 months both in effective group and ineffective group (all P>0.05). CONCLUSIONS: Pain in bones, osteolysis and pathological fracture are the most common clinical manifestations in myeloma-related bone disease. The severity of bone disease can reflect the tumor load, but may not affect the therapeutic effect and the overall survival. The bone metabolic markers tPINP and ß-CTX can be used to evaluate the severity of myeloma-related bone disease at diagnosis and to monitor the effect of treatment for bone disease.