Recombinant human thrombopoietin therapy for primary immune thrombocytopenia in pregnancy: a retrospective comparative cohort study.

BACKGROUND: Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients. AIMS: To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response. METHODS: From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count < 30 × 109/L who did not respond to steroids and/or intravenous immunoglobulin were retrospectively analysed. Of these patients, 33 received rhTPO treatment (rhTPO group) while 48 did not (control group). Baseline characteristics, haematological disease outcomes before delivery, obstetric outcomes, and adverse events were compared between groups. In the rhTPO group, a generalised estimating equation (GEE) was used to investigate the factors influencing the response to rhTPO treatment. RESULTS: The baseline characteristics were comparable between both groups (P > 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5-67.5] vs. 25 [19-29] × 109/L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P < 0.001). Gestational weeks of delivery (37.6 [37-38.4] vs 37.1 [37-37.2] weeks, P = 0.001) were longer in the rhTPO group than in the control group. The rates of caesarean section, postpartum haemorrhage, foetal or neonatal complications, and complication types in both groups were similar (all P > 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment. CONCLUSION: rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.

Curcumin Alleviates Hyperandrogenism and Promotes Follicular Proliferation in Polycystic Ovary Syndrome Rats: Insights on IRS1/PI3K/GLUT4 and PTEN Modulations.

OBJECTIVE: To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS). METHODS: PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 ß-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively. RESULTS: The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05). CONCLUSION: The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.

4-Guanidino-n-butyl syringate (Leonurine, SCM 198) protects H9c2 rat ventricular cells from hypoxia-induced apoptosis.

In the present study, we examined the ability of a chemically synthesized compound based on the structure of leonurine, a phytochemical component of Herba leonuri, to protect H9c2 rat ventricular cells from apoptosis induced by hypoxia and serum deprivation, as a model of ischemia. The results revealed a concentration-dependent increase in cell viability associated with leonurine treatment, accompanied by a consistent decline in lactate dehydrogenase leakage into the culture medium. The fraction of annexin V-fluorescein isothiocyanate-positive cells was increased by hypoxia but reduced by leonurine. These changes were associated with increased expression of the antiapoptotic gene, Bcl-2, and reduced expression of the proapoptotic gene, Bax. Leonurine also reduced the cytosolic Ca overload induced by hypoxia. These results suggest that leonurine elicits potent cardioprotective effects in H9c2 cells, and these effects may be mediated by inhibition of intracellular Ca overload and apoptosis during hypoxia.

Cardioprotective effect of hydrogen sulfide in ischemic reperfusion experimental rats and its influence on expression of survivin gene.

Hydrogen sulfide (H(2)S), as an endogenous gas signaling molecule with important biological function that has been found recently, may play a protection in ischemic reperfusion (I/R) myocardium. We investigated the cardioprotective effect of H(2)S in rats model of ischemic reperfusion in vivo and a probably influence on the expression of survivin, an anti-apoptosis gene. Animals were randomly divided into 3 groups and received either vehicle, sodium hydrosulfide (NaHS) or DL-propargylglycine (PAG) respectively everyday for 1 week before surgery and the treatment continued for a further 2 d after I/R till the animals were sacrificed. We investigated the plasma H(2)S concentration and blood pressure, with the electrocardiogram (ECG) together, to prove the effect of H(2)S to the heart function. We also compared the heart infarct size and the expression of an anti-apoptosis gene, survivin, among groups. As the data shown, the NaHS group had great improvement in blood pressure and electrocardiogram situation. And the remarkable shrink of the infarct size and up-regulation of survivin in NaHS group comparing with the other two groups also showed the cardio protective effect of H(2)S in our study.

Metabolism of Oxidized High Density Lipoprotein-2(ox-HDL(2)) in Rat Hepatic Sinusoidal Cells.

Incubation of rat hepatic sinusoidal cells with FITC-HDL(2), FITC-ox-HDL(2) and [(3)H]CE-HDL(2)(rHDL(2)), ox-rHDL(2) showed that binding of FITC-HDL(2) to the cells was competitive to ox-HDL(2), but not to HDL(2). The cell-endocytic fluorescence strength (FS) of FITC-HDL(2) and radioactivity of ox-rHDL(2) were 45.5% of that of FITC-HDL(2) and 61.4% of that of rHDL(2), respectively. Endocytic FS and radioactivity were mainly in TCA-precipitable and supernatant part, respectively. The cell-released FS and radioactivity were 67.7% and 10.9% of the cell-endocytic FS and the radioactivity, respectively, and both of them were mainly TCA-precipitable. These results suggest that: (1) There is probably an ox-HDL receptor on the surface of rat hepatic sinusoidal cells, which is different from HDL receptor. (2) The metabolic behaviour of ox-rHDL(2) in the cells is similar to HDL(2). Both of them do not take a lysosomal pathway. Apoproteins and CE components dissociate from endocytic lipoprotein in the cells. After the cells have taken up most of CE, the residual CE recombines with apolipoprotein to form a lipoprotein and is released from the cells by retroendocytosis. (3) Oxidative modification of HDL(2) weakens its ability to cholesterol reverse transport.

Cooperation of HDL Receptor and Hepatic Lipase in the Selective Uptake of HDL(2)-CE by Rat Hepatic Sinusoidal Cells.

The recombined (3)H-CE-HDL(2)(rHDL(2)) keeps the biological activities of the native HDL(2). After rat hepatic sinusoidal cells were incubated with rHDL(2) at 37 degrees for 3 h (normal group), the cell-endocytic cpm was 995-/+147(mean-/+s, n=2). After the cells were further incubated for 2 h, the cell-release TCA-precipitable cpm and the TCA-supernatant cpm were 78-/+32 and 12-/+9 respectively. These values were 339-/+62, 19-/+11 and 9-/+5 respectively in the acetylimidazole-modified group, and 542-/+78, 34-/+14 and 9-/+8 respectively in the heparin-pretreated group. Our results suggested that: (1) Rat hepatic sinusoidal cells internalize HDL(2) and take up HDL(2)-CE by its HDL receptor, and HDL(3) was secreted out of the cells by retroendocytosis. (2) Hepatic lipase (HL) induces directly the selective uptake of HDL(2)-CE by the cells. (3) There is cooperation between the HDL receptor and HL in the selective uptake of HDL(2)-CE by the cells.