Development and validation of risk score for predicting spontaneous rupture of hepatocellular carcinoma

Purpose@#Spontaneous rupture is a potentially serious complication of liver cancer. A risk score was developed and validated for predicting spontaneous rupture based on a retrospective study. @*Methods@#Multiple logistic regression analysis was used to study the relationship between clinical variables and spontaneous rupture. The independent rupture predictors were converted into a score based on the odds ratio. Predicted attributes of the developed scores were then verified using a dataset in 2019. @*Results@#The incidence of spontaneous rupture was 5.5% from 2002 to 2019. A 10-point score (α-FP of ≥400 μg/L, 1; protrusion from liver surface, 2; ascites, 3; tumor size of >5 cm, 4) was derived for prediction of rupture and area under the receiver-operating characteristic curve was 0.9 (95% confidence interval, 0.87–0.92). When applying a cutoff value of 5 points or more, the specificity was 0.87 and the sensitivity was 0.84. A validation cohort consisting of 202 hepatocellular carcinoma patients reproduces the predictive, identification, and calibration characteristics. The observed rate of spontaneous rupture according to risk stratification of the score was 0.6% for those with a score of 0–4, 21.6% for a score of 5–7, and 36.4% for a score of 8–10 in the validation cohort. @*Conclusion@#Here, based on routine clinical data, we determine the factors that affect prognosis and propose an effective tool for predicting spontaneous rupture, which may be useful in guiding priority treatment of high-risk patients or clinical routine preventive treatment.

Research progress in drug therapy for bronchopulmonary dysplasia in preterm infants / 中国当代儿科杂志

Bronchopulmonary dysplasia (BPD) is the most common long-term complication in surviving extremely preterm infants. This may lead to pulmonary hypertension, increase late neonatal mortality, and cause abnormal neural development. There is still controversy over the efficacy, as well as advantages and disadvantages, of drug therapy for BPD in preterm infants. This article reviews the research progress in the drug therapy for BPD.

ROCK1 and the relative signal molecules participate in proliferation of vascular smooth muscle cells induced by cyclic strain / 医用生物力学

Objective To investigate the role of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) and the relative signal molecules in sensing the mechanical stimulation from tensile strain and regulating the proliferation of vascular smooth muscle cells (VSMCs).Methods Physiological cyclic strain with magnitude of 10％ and at frequency of 1.25 Hz was applied to VSMCs in vitro by using the strain loading system.The proliferation level of VSMCs was analyzed by BrdU ELISA;the expression level of ROCK1,phosphorylations of protein kinase C (PKC) α/β Ⅱ,protein kinase D (PKD) and extracellular regulated protein kinase (ERK) in VSMCs modulated by cyclic strain were detected with Western blotting;the expression of ROCK1 was specifically repressed by using RNA interference (RNAi).Results Compared with the static control,10％ cyclic strain significantly decreased the expression of ROCK1 and phosphorylations of PKD and ERK.The phosphorylation of PKCα/βⅡ decreased significantly under 10％ cyclic strain for 12 h,but returned to normal level after loading for 24 h.Repressed expression of ROCK1 with RNAi significantly down-regulated VSMC proliferation,suppressed phosphorylations of PKCα/βⅡ and PKD,but no obvious changes were found in phosphorylation of ERK.Conclusions Physiological cyclic strain with magnitude of 10％ may repress the phosphorylation of PKCα/βⅡ and PKD via inhibiting the expression of ROCK1,and subsequently affects VSMC proliferation and maintains vascular hemostasis.The investigation on intracellular mechanotransduction network of VSMCs under mechanical stimulation of cyclic strain may contribute to studying the physiological and pathological mechanisms of cardiovascular diseases.

ROCK1 and the relative signal molecules participate in proliferation of vascular smooth muscle cells induced by cyclic strain / 医用生物力学

Objective To investigate the role of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) and the relative signal molecules in sensing the mechanical stimulation from tensile strain and regulating the proliferation of vascular smooth muscle cells (VSMCs).Methods Physiological cyclic strain with magnitude of 10％ and at frequency of 1.25 Hz was applied to VSMCs in vitro by using the strain loading system.The proliferation level of VSMCs was analyzed by BrdU ELISA;the expression level of ROCK1,phosphorylations of protein kinase C (PKC) α/β Ⅱ,protein kinase D (PKD) and extracellular regulated protein kinase (ERK) in VSMCs modulated by cyclic strain were detected with Western blotting;the expression of ROCK1 was specifically repressed by using RNA interference (RNAi).Results Compared with the static control,10％ cyclic strain significantly decreased the expression of ROCK1 and phosphorylations of PKD and ERK.The phosphorylation of PKCα/βⅡ decreased significantly under 10％ cyclic strain for 12 h,but returned to normal level after loading for 24 h.Repressed expression of ROCK1 with RNAi significantly down-regulated VSMC proliferation,suppressed phosphorylations of PKCα/βⅡ and PKD,but no obvious changes were found in phosphorylation of ERK.Conclusions Physiological cyclic strain with magnitude of 10％ may repress the phosphorylation of PKCα/βⅡ and PKD via inhibiting the expression of ROCK1,and subsequently affects VSMC proliferation and maintains vascular hemostasis.The investigation on intracellular mechanotransduction network of VSMCs under mechanical stimulation of cyclic strain may contribute to studying the physiological and pathological mechanisms of cardiovascular diseases.

ROCK1 and the relative signal molecules participate in proliferation of vascular smooth muscle cells induced by cyclic strain / 医用生物力学

Objective To investigate the role of rho-associated coiled-coil containing protein kinase 1 (ROCK1) and the relative signal molecules in sensing the mechanical stimulation from tensile strain and regulating the proliferation of vascular smooth muscle cells (VSMCs). Methods Physiological cyclic strain with magnitude of 10% and at frequency of 1.25 Hz was applied to VSMCs in vitro by using strain loading system. The proliferation level of VSMCs was analyzed by BrdU ELISA; the expression level of ROCK1, phosphorylations of protein kinase C (PKC) α/β II, protein kinase D (PKD) and extracellular regulated protein kinase (ERK) in VSMCs modulated by cyclic strain were detected with Western blotting; the expression of ROCK1 was specifically repressed by using RNA interference (RNAi). Results Compared with the static control, 10% cyclic strain significantly decreased the expression of ROCK1 and phosphorylations of PKD and ERK. The phosphorylation of PKCα/βII was decreased significantly under 10% cyclic strain for 12 h, but returned to normal level after 24 h-loading. Repressed expression of ROCK1 with RNAi significantly down-regulated VSMC proliferation, suppressed phosphorylations of PKCα/βII and PKD, but no obvious change was found in phosphorylation of ERK. Conclusions Physiological cyclic strain with magnitude of 10% may repress the phosphorylation of PKCα/βII and PKD via inhibiting the expression of ROCK1, which subsequently affect VSMC proliferation and maintain vascular hemostasis. The investigation on intracellular mechanotransduction network of VSMCs under mechanical stimulation of cyclic strain may contribute to the physiological and pathological mechanisms of cardiovascular diseases.

The role of FOXO1 in cyclic stretch induced-proliferation of vascular smooth muscle cells during hypertension / 医用生物力学

Objective To investigate the role of pathologically increased-cyclic stretch in proliferation of vascular smooth muscle cells (VSMCs) during hypertension, and the effect of Forkhead box protein O1 (FOXO1) during this process. Methods Coarctation of abdominal aorta above kidney artery of rat was used as hypertensive animal model, and sham-operated animal as control. FX-4000 cyclic stretch loading system was used to apply 5% physiologically cyclic stretch and 15% pathologically cyclic stretch during hypertension on VSMCs in vitro. Western blot was used to reveal the expressions of FOXO1 and phosphor-FOXO1 in VSMCs, and BrdU kit to detect the proliferation of VSMCs in vitro. By using RNA interference in static, the role of FOXO1 on cell proliferation was further detected. Results After abdominal aorta coarctation for 2 and 4 weeks, respectively, the blood pressure was significantly increased compared with the sham operated rats. The proliferation of vascular cells in aorta of hypertensive rat was significantly increased, and so did the expressions of FOXO1 and phosphor-FOXO1. In vitro experiment revealed that 15% cyclic stretch remarkably increased the proliferation and expressions of FOXO1 and phospho FOXO1 in VSMCs. Target siRNA transfection in static decreased the expression of FOXO1 and phosphor-FOXO1, as well as the proliferation of VSMCs. Conclusions Pathologically increased-cyclic stretch may increase the expression and phosphorylation of FOXO1, subsequently modulate VSMC proliferation during hypertension. Based on animal models, this study intends to reveal the role of FOXO1 in vascular reconstruction of hypertension and the involved biomechanical mechanism, so as to make the mechanobiological mechanism of hypertension explicit and discover new target in the prevention and treatment of vascular remodeling.

Shear stress modulates the proliferation of vascular smooth muscle cells via receptor for activated C kinase 1 / 医用生物力学

Objective To investigate the role of receptor for activated C kinase 1 (RACK1) in vascular smooth muscle cells (VSMCs) proliferation modulated by co-cultured endothelial cells (ECs) and shear stress. Methods Using EC/VSMC co-cultured parallel plate flow chamber system, two levels of shear stress, i.e. low shear stress (LowSS, 0.5 Pa) and normal shear stress (NSS, 1.5 Pa), were applied for 12 h. BrdU ELISA was used to detect the proliferation of VSMCs, and Western blot was used to detect the protein expressions of RACK1 and phosphor-Akt. Under the static condition, RNA interference was used to suppress the expression of RACK1 in VSMCs, and then the proliferation of VSMCs and expressions of RACK1 and phosphor-Akt were detected. By using co-culture model (ECs/VSMCs) and separated culture model (ECs//VSMCs), the effect of ECs on expressions of RACK1 and phosphor-Akt in VSMCs was further analyzed. Results Comparative proteomic analysis revealed that LowSS increased the expression of RACK1 in rat aorta. In vitro experiments showed that LowSS induced the proliferation, expressions of RACK1 and phospho Akt in VSMCs co-cultured with ECs. Target RNA interference of RACK1 significantly decreased the proliferation of VSMCs, and the phosphorylation of Akt. In comparison with ECs//VSMCs (separated culture) group, the expression of RACK1 and phosphor-Akt were both up-regulated in the VSMCs co-cultured with ECs (ECs/VSMCs group). Conclusions The expression of RACK1 in VSMCs was modulated by shear stress and neighboring ECs, which might induce cellular proliferation via PI3K/Akt pathway. The investigation on VSMC proliferation and the involved biomechanical mechanism will contribute to understanding and help preventing the pathogenesis and progress of atherosclerosis.