Post-acute pancreatitis diabetes mellitus (PPDM-A) is a common type of exocrine pancreatic diabetes. It is very important to clarify the risk factors of PPDM-A and effectively screen for diabetes in patients with acute pancreatitis to prevent the occurrence and development of PPDM-A. This article elaborates on the three aspects of PPDM-A, including high-risk population, screening timing and methods, as well as PPDM-A screening in children and adolescents, aiming to provide a basis for early detection of PPDM-A and timely targeted treatment for patients.

Post-acute pancreatitis diabetes mellitus (PPDM-A) is a common type of exocrine pancreatic diabetes. It is very important to clarify the risk factors of PPDM-A and effectively screen for diabetes in patients with acute pancreatitis to prevent the occurrence and development of PPDM-A. This article elaborates on the three aspects of PPDM-A, including high-risk population, screening timing and methods, as well as PPDM-A screening in children and adolescents, aiming to provide a basis for early detection of PPDM-A and timely targeted treatment for patients.

OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China.METHODS By reviewing initiatives and experiences from the United States(U.S.),European Union(EU),and Japan in promoting patient engagement,this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally.Combining China's current progress and challenges in patient engagement,specific proposals are formulated to refine regulatory pathways and institutional systems.RESULTS&CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy,countries or regions such as the U.S.,EU,and Japan have established clear policies,designated oversight agencies,and developed diversified pathways for patient engagement.Patients contribute to regulatory processes through advisory meetings,direct decision-making roles,and leveraging lived experiences and expertise to optimize drug evaluation and monitoring.In contrast,China's patient engagement remains primarily limited to clinical value-oriented drug development,lacking formal policy guidance.It is recommended that China,based on its existing policy system,further strengthen the construction of a safeguard system for patient engagement,improve the capacity building and pathway models for patient participation in pharmaceutical regulation,and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

Objective To evaluate the effect of a protein kinase CK2 inhibitor on intracellular levels of reactive oxygen species and DNA double?stand break in human non?small cell lung cancer H460 cells. Methods H460 cells were exposed to 0, 12?5, 25.0, and 50.0μmol/L quinalizarin, a specific inhibitor of protein kinase CK2, for 24 hours. The changes in protein and mRNA levels of CK2 subunits were measured. Flow cytometry was used to measure changes in the intracellular levels of reactive oxygen species in H460 cells after 4 or 24 hours of quinalizarin treatment. Immunofluorescence assays were performed to determine the effect of the CK2 inhibitor onγ?H2 AX expression and the average fluorescent number ofγ?H2 AX foci in H460 cells. Comparison was made by analysis of variance and t test. Results There were no significant differences in protein or mRNA levels of CK2 subunits in H460 cells after quinalizarin treatment ( CK2α,0μmol vs. 12?5 μmol/L, P=0?966;0 μmol/L vs. 25 μmol/L, P=0?355;0 μmol/L vs. 50 μmol/L, P=0?864, CK2α’ , 0 μmol/L vs. 12?5μmol/L,P=0?409;0μmol/L vs. 25μmol/L,P=0?833;0μmol/L vs. 50 μmol/L, P=0?0. 746, CK2β, 0 μmol/L vs. 12?5 μmol/L, P=0?532;0 μmol/L vs. 25 μmol/L, P=0?830;0 μmol/L vs. 50 μmol/L, P= 0?061 ) . The intracellular levels of reactive oxygen species were substantially elevated in H460 cells with the increase in quinalizarin concentration and treatment time. Different concentrations of quinalizarin resulted in dose?and time?dependent increases in the numbers of γ?H2 AX foci after 4 and 24 hours of treatment ( treated by Quianlizarin for 4 or 24 h, 0 μmol/L vs. 12?5μmol/L,12?5 μmol/L vs. 25 μmol/L, 25 μmol/L vs. 50 μmol/L, all P=0?000, concentration is 12?5μmol/L,25 μmol/L or 50 μmol/L, 4 h vs. 24 h, all all P=0?000 ) . Conclusions Quinalizarin can increase the intracellular levels of reactive oxygen species and DNA double?stand break in H460 cells by inhibition of protein kinase CK2 activity. This study provides a theoretical basis for using quinalizarin as a potential radiosensitizer for lung cancer.

[Abstr act] Objective To explore whether quninalizarin, an specific inhibitor of protein kinase CK2, could sensitize icotinib in EGFR-TKIs (epithelial growth factor receptor-tyrosine kinase inhibitor)-resistant cell lines and uncover the underlying mechanisms.Methods MTT assay was performed to evaluate the inhibitory effect of quninalizarin, icotinib or the combination of both on cell proliferation in several lung adenocarcinoma cell lines.Western blot assay was used to assess if combined inhibition of EGFR and protein kinase CK2 by icotinib and quninalizarin, exerts effect on the expression and phosphorylation of major proteins of EGFR signaling pathways.Results The IC50 of HCC827, H1650 , H1975 and A549 cells for icotinib were (8.07±2.00) μmol/L, (66.01±6.64) μmol/L, (265.60±9.47) μmol/L and( 87.88±6.8)μmol/L, respectively, indicating that HCC827 cells are sensitive to icotinib, and the H1650, H1975 and A549 cells are relatively resistant to icotinib.When treated with both quninalizarin and icotinib in the concentration of 50 μmol/L, the viability of H1650, H1975 and A549 cells was (40.64±3.73)%, (65.74± 3.27)% and (44.96±0.48)%, respectively, significantly lower than that of H1650 , H1975 and A549 cells treated with 50 μmol/L icotinib alone (55.05±1.22)%, (71.98±1.60)% and (61.74±6.18)%, respectively (P<0.01 for all).When treated with both 100 μmol/L quninalizarin and 100 μmol/L icotinib, the viability of H1650, H1975and A 549 ells were (23.35±0.81)%, (55.70±1.03)%, (33.42±1.33)%,respectively, significantly lower than the viability of H1650, H1975 and A549 cells treated with 100 μmol/L icotinib alone (40.57±2.65)%, (62.40±2.05)% and (44.97±8.20)%, respectively, (P<0.01 for all).The two-way ANOVA analysis showed that compared with the viability of EGFR-TKIs-resistant cells ( H1650, H1975, A549) treated with 50 μmol/L and 100 μmol/L icotinib alone, the viability of cells treated with icotinib and quinalizarin were significantly suppressed, and the differences were statistically significant (P<0.01).In addition, the phosphorylation form of Akt and ERK (namely p-Akt and p-ERK) were significantly down-regulated by treating with quninalizarin and icotinib together in the H1650 cells while the expression of Akt and ERK changed little.Conclusions Quinalizarin, as a specific CK2 inhibitor, may overcome icotinib resistance by inhibiting proliferation mediated by Akt and ERK in human lung adenocarcinoma cell lines, and enhances the suppressive effect of icotinib on the proliferation of EGFR-TKIs-resistant human lung adenocarcinoma cells.

[Abstr act] Objective To explore whether quninalizarin, an specific inhibitor of protein kinase CK2, could sensitize icotinib in EGFR-TKIs (epithelial growth factor receptor-tyrosine kinase inhibitor)-resistant cell lines and uncover the underlying mechanisms.Methods MTT assay was performed to evaluate the inhibitory effect of quninalizarin, icotinib or the combination of both on cell proliferation in several lung adenocarcinoma cell lines.Western blot assay was used to assess if combined inhibition of EGFR and protein kinase CK2 by icotinib and quninalizarin, exerts effect on the expression and phosphorylation of major proteins of EGFR signaling pathways.Results The IC50 of HCC827, H1650 , H1975 and A549 cells for icotinib were (8.07±2.00) μmol/L, (66.01±6.64) μmol/L, (265.60±9.47) μmol/L and( 87.88±6.8)μmol/L, respectively, indicating that HCC827 cells are sensitive to icotinib, and the H1650, H1975 and A549 cells are relatively resistant to icotinib.When treated with both quninalizarin and icotinib in the concentration of 50 μmol/L, the viability of H1650, H1975 and A549 cells was (40.64±3.73)%, (65.74± 3.27)% and (44.96±0.48)%, respectively, significantly lower than that of H1650 , H1975 and A549 cells treated with 50 μmol/L icotinib alone (55.05±1.22)%, (71.98±1.60)% and (61.74±6.18)%, respectively (P<0.01 for all).When treated with both 100 μmol/L quninalizarin and 100 μmol/L icotinib, the viability of H1650, H1975and A 549 ells were (23.35±0.81)%, (55.70±1.03)%, (33.42±1.33)%,respectively, significantly lower than the viability of H1650, H1975 and A549 cells treated with 100 μmol/L icotinib alone (40.57±2.65)%, (62.40±2.05)% and (44.97±8.20)%, respectively, (P<0.01 for all).The two-way ANOVA analysis showed that compared with the viability of EGFR-TKIs-resistant cells ( H1650, H1975, A549) treated with 50 μmol/L and 100 μmol/L icotinib alone, the viability of cells treated with icotinib and quinalizarin were significantly suppressed, and the differences were statistically significant (P<0.01).In addition, the phosphorylation form of Akt and ERK (namely p-Akt and p-ERK) were significantly down-regulated by treating with quninalizarin and icotinib together in the H1650 cells while the expression of Akt and ERK changed little.Conclusions Quinalizarin, as a specific CK2 inhibitor, may overcome icotinib resistance by inhibiting proliferation mediated by Akt and ERK in human lung adenocarcinoma cell lines, and enhances the suppressive effect of icotinib on the proliferation of EGFR-TKIs-resistant human lung adenocarcinoma cells.