Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.

Background: Patent ductus arteriosus (PDA) remains a common congenital heart disease in pediatric patients, and the new trend of catheterization therapy is still associated with some potential risks and complications. Hypothesis: Compared with surgical closure, the clinical effect of catheterization therapy in pediatric PDA patients requires meta-analysis. Methods: A systematic literature search of PubMed, Cochrane Library, Embase, Science Citation Index, Web of Science, and the Chinese Biomedicine literature database was conducted. Eligible studies included controlled trials of pediatric PDA patients receiving catheterization therapy vs surgical closure. Relative risks (RRs), standard mean differences, and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I 2 test. Results: Seven studies with a total of 810 patients met the inclusion criteria. Catheterization therapy neither significantly increased the primary success rate (RR: 0.92, 95% CI: 0.82-1.03, P = 0.16) nor reduced the total postprocedure complications (RR: 0.74, 95% CI: 0.44-1.25, P = 0.26) and blood transfusion (RR: 1.10, 95% CI: 0.16-7.67, P = 0.93). Catheterization was associated with a statistically significant increase in residual shunts (RR: 5.19,, P = 0.01) and reduction in length of hospital stay (standard mean difference: −1.66, 95% CI: −2.65 to −0.67, P = 0.001). Conclusions: Catheterization therapy in pediatric PDA patients did not show a significant advantage in primary success rate, total complications, or blood transfusion, but it was associated with increase in residual shunts and reduction in length of hospital stay.

Primary central nervous system lymphoma (PCNSL) is aggressive and confined to the central nervous system, including the brain parenchyma, leptomeninges, spinal cord, eyes or cranial nervous. Morphologically, approximately 95% of these tumors are DLBCL according to the new World Health Organization (WHO) classification. However, PCNSL has treatment outcome distinct from those of systemic DLBCL, as well as dismal prognosis than systemic DLBCL. Our goal was to determine the immunohistochemical profile and prognostic significance for 132 Chinese PCNSL cases. The expression of CD20, CD10, BCL-6, MUM1, CD138, BCL-2, and Ki67 antigens were observed by immunohistochemical method. All cases expressed CD20. CD10, BCL-6, and MUM1 were positive in 15.2% (20/132), 86.4% (114/132), 90.2% (119/132). CD138 was negative in 100% (39/39). BCL-2 was positive in 89.3% (108/121). The Ki67 antigen, a proliferative index, ranging from 1% to 100% (median 85.3%) and 76.5% (101/132) PCNSLs showed Ki67 ≥ 90%. Among 132 cases, 25 (18.9%) were classified as germinal center B-cell-like (GCB); 107 (81.1%) were classified as activated B-cell-like (ABC). The Ki67 index in 25 GCB was similar to that in 107 ABC (p=0.663>0.05). No significant correlation was found between Ki67 index and BCL-2 (p=0.225>0.05). Significant positive correlation was found between Ki67 index and BCL-6 expression (p=.000<0.05). Among 132 cases, 43 had complete data of treatment that received chemotherapy regimens based on HD-MTX. GCB and ABC had similar OS (p=0.969) and PFS (p=0.070). These findings support that PCNSL predominantly express an ABC immunophenotype and express high Ki67 index, and suggest that the proliferative activity of GCB was similar to ABC and the expression of BCL-6 but not BCL-2 was positively correlated with the malignant degree of tumors. Table 1. Clinical characteristics. Characteristics Patients, n (%) Age (years); n=132 ≥60 y, n=53; <60 y, n=79 Median (range) 57 (21-85) Gender; n=132 Male 69 (52.3) Female 63 (47.7) ECOG; n=43 0-1 8 (18.6) 2-4 35 (81.4) LDH; n=43 Normal 25 (58.1) Elevated 18 (41.9) Numbers of lesions; n=132 1 48 (36.4) >2 84 (63.6) Involvement of deep structures; n=132 Absence 43 (32.6) Presence 89 (67.4) Table 2. Hans classification. CD10 BCL-6 MUM1 Immunoprofile PCNSL, n (%) + + + GCB 16 (12.1) + + - GCB 3 (2.3) + - + GCB 0 (0) + - - GCB 1 (0.7) - + - GCB 5 (3.8) - + + Non-GCB 90 (68.2) - - + Non-GCB 12 (9.1) - - - Non-GCB 5 (3.8) Table 3. Chang classification. CD10 BCL-6 MUM1 Immunoprofile PCNSL, n (%) + + - GCB (Pattern A) 3 (2.4) + - - GCB (Pattern A) 1 (0.8) - + - GCB (Pattern A) 5 (3.9) + + + activated GCB (Pattern B) 16 (12.6) + - + activated GCB (Pattern B) 0 (0) - + + activated GCB (Pattern B) 90 (70.9) - - + activated non-GCB (Pattern C) 12 (9.4) Figure 1. Immunohistochemical labeling. Figure 1. Immunohistochemical labeling. Figure 2. Kaplan-Meier curve shows clinical prognostic variables and their relationship to OS and/or PFS. Figure 2. Kaplan-Meier curve shows clinical prognostic variables and their relationship to OS and/or PFS. Figure 3. T1 axial, post-gadolinium magnetic resonance imaging of PCNSL. Figure 3. T1 axial, post-gadolinium magnetic resonance imaging of PCNSL. Disclosures No relevant conflicts of interest to declare.