Defects in myocyte contraction and relaxation are key features of human heart failure. Sodium/calcium exchanger-mediated contribution to contraction and relaxation were separated from other mechanisms [L-type calcium current, sarco(endo)plasmic reticulum (SR) Ca2+-ATPase] based on voltage, temperature, and selective blockers. Rod-shaped left ventricular myocytes were isolated from failed human explants ( n = 29) via perfusion with collagenase-containing Krebs solution. Action potentials using perforated patch and contractions using an edge detector were recorded at 0.5–1.5 Hz in Tyrode solution at 25°C and 37°C. Contraction duration was dependent on action potential (AP) duration at 37°C but not at 25°C, suggesting the role of the exchanger in relaxation and linking myocyte relaxation to the repolarization phase of the AP. Voltage-clamp experiments from −50 to +10 mV for 1,500 ms in Tyrode or Na+- and K+-free solutions after conditioning pulses triggered biphasic contractions that included a rapid SR-mediated component and a slower voltage-dependent exchanger-mediated component. We used thapsigargin to block the SR, which eliminated the rapid component, and we used an exchanger blocker, Kanebo 7943, which eliminated the slow component. The exchanger was shown to contribute to contraction through reverse-mode exchange, as well as to play a key role in relaxation of human ventricular myocytes.

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ObjectiveThe purpose of this study was to determine the association between PD1 expression and the clinical prognosis of diffuse large B-cell lymphoma (DLBCL) co-occurring with hepatitis B virus (HBV) infection.MethodsA total of 165 patients presented with newly diagnosed and untreated DLBCL at the First Hospital of Jilin University, Changchun, China, between 2011.01 and 2014.12. Complete clinical information was available for 152 of these 165 patients. We retrospectively reviewed the results of HBV serum marker assays and the clinical information of these 152 DLBCL patients from our hospital database; eventually, only 51 patients were enrolled in this study, and these 51 patients received the PD1 test item.Results① The incidence of HBsAg prevalence was 13.2% (20/152) in this study; ② The incidence of PD1 expression in the HBsAg+ group was 4.3-fold higher than that in the HBsAg—group (40.0% vs 9.4%; P = 0.010); ③ The clinical information, including sex, age, clinical stage, IPI, molecular subtype and chemotherapy status, was analyzed between the HBsAg+ and HBsAg—groups, but there were no significant differences between the two groups; ④ The median OS and PFS of the patients in the HBsAg+ group were 36.5 months and 12 months, respectively; however, the median OS and PFS of patients in the HBsAg—group were not reached (P = 0.033) and 32 months (P = 0.049), respectively; and ⑤ The median OS and PFS of PD1-positive patients in the HBsAg+ group were the worst (24 months and 9 months, respectively), whereas the median OS and PFS of PD1-negative patients in the HBsAg—group were the best (not reached and 32 months, respectively).ConclusionsCompared with patients in the HBsAg—group, the incidence of PD1 expression was significantly higher in the HBsAg+ group, and the median OS and PFS times were the worst in PD1-positive patients in the HBsAg+ group. These results indicated that the dismal prognosis of patients with HBsAg+ may be related to the high rate of PD1 expression. Thus, a targeted PD1 treatment strategy may improve the prognosis of HBsAg+ DLBCL patients.

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