Objective:To discuss the influence and curative effect of intensive lipid-lowering with atorvastatin on blood fat and ser-um inflammatory factors levels in the patients with acute cerebral infarction. Methods:Totally 94 cases of patients with acute cerebral infarction were divided into the intensive group(n=47) and the ordinary group (n=47). The patients in the two groups were given the basic medical treatment, such as reducing intracranial pressure and dehydration, controlling blood pressure and blood sugar, anti-platelet aggregation, neural protection and etc. The patients in the ordinary group were orally given 20mg atorvastatin calcium tablets, once a day, while the patients in the intensive group were additionally given 40mg atorvastatin calcium tablets, once a day, and the treatment course was 8 weeks. The changes of blood fat index and serum inflammatory factors of hs-CRP, TNF-αand IL-10 in the two groups before and after the medical treatment were detected, and the clinical curative effect was compared as well. Results:After the 8-week medical treatment, TC, TG and LDL-C levels in the two groups were declined at different degree, while HDL-C levels were in-creased at different degree (P<0. 05 or P<0. 01), and the changes in the intensive group was more notable than those in the ordinary group (P<0. 05). After the treatment, the serum hs-CRP and TNF-αlevels in the two groups were declined at different degree, while serum IL-10 levels were increased at different degree (P<0. 05 or P<0. 01), and the changes in the intensive group was more signifi-cant than those in the ordinary group (P<0. 05). Meanwhile, the total clinical efficiency in the intensive group (95. 74%) was much higher than that in the ordinary group (80. 85%, P<0. 05). Respectively 2 and 4 cases of untoward effect were appeared in the ordi-nary group and the intensive group without statistical difference between the two groups(P>0. 05). Conclusion:Intensive lipid-lower-ing with atorvastatin has significant curative effect with favorable security on acute cerebral infarction, which can obviously improve the degree of neural function defect, and the mechanism may related with reducing blood fat, serum hs-CRP and TNF-αlevels, increasing serum IL-10 levels and inhibiting topical inflammatory reactions.

Currently, several major challenges still exist in liver transplantation for hepatocellular carcinoma (HCC), including the opportunity of liver transplantation for HCC patients beyond selection criteria, drop-out from the waiting list for HCC patients within selection criteria due to tumor progression and the tumor recurrence after liver transplantation. In recent years, revolutionary efficacy has been achieved in treating advanced HCC by employing systemic drugs, such as lenvatinib and systemic drug-based comprehensive treatment, which also sheds light on the down-staging therapy and bridging therapy for HCC patients listed for liver transplantation, and prevention and treatment of tumor recurrence after liver transplantation for HCC individuals. Systemic drug-based comprehensive treatment probably has the potential to improve the clinical efficacy of liver transplantation for HCC, which deserves in-depth investigation. In this review, we summarize the progress on down-staging therapy, bridging therapy as well as prevention and treatment of tumor recurrence after liver transplantation for HCC individuals, aiming to provide reference for clinical managementof HCC.

Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.

Objective To verify whether β-arrestin-2 inhibits autophagy by up-regulating PI3K/Akt signal to protect the liver from ischemia-reperfusion injury (IRI) in mice. Methods Twelve β-arrestin-2 knockout (KO) and twelve wild-type (WT) C57BL/6 mice were randomly divided into the KO+sham group, KO+IRI group, WT+sham group and WT+IRI group, six mice in each group. The mouse models with 70% liver IRI were established or sham operation was performed. Relevant experiments were carried out at 6 h after liver reperfusion or operation. The expression levels of apoptosis signal protein cleaved Caspase-3, proliferation signal protein Ki-67 and the PI3K/Akt signal protein p-Akt were detected by immunohistochemical staining. Results Immunohistochemical staining demonstrated that compared with the corresponding sham group, the positive cell count for cleaved Caspase-3, Ki-67 and p-Akt in liver tissues of mice was significantly increased in the KO+IRI and WT+IRI groups (all P < 0.01). Compared with the WT+IRI group, the positive cell count for cleaved Caspase-3 in liver tissues of mice was significantly increased, whereas the positive cell count forKi-67 and p-Akt was significantly decreased in the KO+IRI group (both P < 0.05). Conclusions β-arrestin-2 can mitigate the liver cell apoptosis and promote the repair of injury after IRI in mice. Moreover, β-arrestin-2 inhibits autophagy by up-regulating the PI3K/Akt signal to alleviate liver IRI in mice.

Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective To investigate the causes, prevention and treatment of seizures following liver transplantation (LT). Methods In the 772 patients undergoing LT in Organ Transplantation Center, the third Affiliated Hospital of Sun Yat-sen University from October 2003 to June 2009, clinical data of 8 patients who developed seizures during the follow-up after operation were analyzed retrospectively. The informed consents of all patients were obtained and the ethical committee approval was received. There were 5 males and 3 females with age ranging from 46 to 58 years old and median age of 54 years old. The patients received regular reexaminations of blood routine, liver function, renal function, electrolytes, blood concentration of immunosuppressant, infection related etiological examinations, etc. The examinations of electroencephalogram (EEG), computed tomography (CT), or magnetic resonance imaging (MRI) were completed for the suspicious patients of seizures. The causes of disease, diagnosis, treatments and outcome of the patients were analyzed, including the incidence, onset time, seizures types, etiological analysis, treatments and outcome. Results The incidence of seizures following LT was 1.0% (8/772), in which 1 case occurred in 1 week after operation, 2 cases within 5 to 6 weeks, 5 cases over 16 weeks and the longest case over 7 years after operation. Generalized tonic-clonic seizure was observed in 7 cases, including 2 cases developed to status epilepticus and 1 case of complex partial seizure. The etiological analysis revealed that 1 case had a history of seizures and 2 cases had hepatic encephalopathy before operation. Water-electrolyte imbalance occurred in 6 cases after operation including 2 cases complicated with hypoglycemia. And cerebral apoplexy occurred in 4 cases after operation including 1 case complicated with abnormally elevating blood concentration of tacrolimus (FK506), 1 case complicated with intracranial fungus and cytomegalovirus infections. Sedative and antiepileptic were given to all of 8 patients and various inducements were treated. Two cases recovered well and were discharged from hospital, and 6 cases died of multiple organ dysfunction syndrome or cerebral hemorrhage. Conclusions Seizures following LT may be related with many factors such as preoperative history of seizures and hepatic encephalopathy, immunosuppressant toxicity, water-electrolyte imbalance, cerebral apoplexy and intracranial infections after operation, etc. Once seizures are confirmed, sedative and antiepileptic should be given to the patients and various inducements should be treated. The prognosis of the patients is poor.

Objective To evaluate the safety and efficacy of individualized treatment of splenorenal shunt during liver transplantation. Methods Clinical data of 2 recipients who underwent orthotopic liver transplantation and splenorenal shunt intraoperatively were retrospectively analyzed. According to the perfusion status after splenorenal shunt and donor liver reflow, the left renal vein ligation and splenorenal shunt vessel ligation were performed in two recipients during liver transplantation. The general postoperative conditions of the recipients were observed, including surgical related complications, peak portal blood flow velocity, liver and renal function indexs. The postoperative conditions of the recipients were monitored by abdominal ultrasound. Results No intraoperative or postoperative complications occurred in two recipients. The changes of peak portal blood flow velocity before and after splenorenal shunt in two recipients were 22.9-35.1 cm/s and 24.3-58.8 cm/s respectively. No delayed recovery of alanine aminotransferase (ALT) level was observed in two patients after operation. Case 1 experienced a transient increase in the serum creatinine (Scr), which was recovered to normal at postoperative 13 d. During the postoperative follow-up, ultrasound examination demonstrated that the direction and velocity of portal blood flow were normal and liver perfusion was excellent. Conclusions It is safe and effective to selectively ligate the left renal vein or splenorenal shunt vessels of the recipients with severe splenorenal shunt during liver transplantation.