In situ subtotal spleen resection combined with selective pericardial devascularization for the treatment of portal hypertension.

BACKGROUND: Hypersplenism and esophageal varices bleeding are the major complications of portal hypertension (PHT). In recent years, increasing attention has been given to spleen preservation operations. The mode and long-term effects of subtotal splenectomy and selective pericardial devascularization for PHT remain controversial. AIM: To investigate the clinical efficacy and safety of subtotal splenectomy combined with selective pericardial devascularization for the treatment of PHT. METHODS: This was a retrospective study of 15 patients with PHT who underwent subtotal splenectomy not preserving the splenic artery or vein combined with selective pericardial devascularization in the Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University from February 2011 to April 2022. Fifteen propensity score-matched patients with PHT who underwent total splenectomy at the same time served as the control group. The patients were followed for up to 11 years after surgery. We compared the postoperative platelet levels, perioperative splenic vein thrombosis, and serum immunoglobulin levels between the two groups. Abdominal enhanced computed tomography was used to evaluate the blood supply and function of the residual spleen. The operation time, intraoperative blood loss, evacuation time, and hospital stay were compared between the two groups. RESULTS: The postoperative platelet level of patients in the subtotal splenectomy group was significantly lower than that in the total splenectomy group (P < 0.05), and the postoperative portal system thrombosis rate in the subtotal splenectomy group was also much lower than that in the total splenectomy group. The levels of serum immunoglobulins (IgG, IgA, and IgM) showed no significant differences after surgery compared with before surgery in the subtotal splenectomy group (P > 0.05), but serum immunoglobulin IgG and IgM levels decreased dramatically after total splenectomy (P < 0.05). The operation time in the subtotal splenectomy group was longer than that in the total splenectomy group (P < 0.05), but there were no significant differences in the amount of intraoperative blood loss, evacuation time, or hospital stay between the two groups. CONCLUSION: Subtotal splenectomy not preserving the splenic artery or vein combined with selective pericardial devascularization is a safe and effective surgical treatment for patients with PHT, not only correcting hypersplenism but also preserving splenic function, especially immunological function.

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES: We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS: Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS: HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.

Functional predication of differentially expressed circRNAs/lncRNAs in the prefrontal cortex of Nrf2-knockout mice.

In the central nervous system, nuclear factor erythroid-2-related factor 2 (Nrf2) protects neurons from oxidant injury, thereby ameliorating neurodegeneration. We explored the key circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) involved in Nrf2-induced neuroprotection. We used microarrays to examine the circRNAs (DEcircRNAs), lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) differentially expressed between Nrf2 (+/+) and Nrf2 (-/-) mice and identified DEcircRNA/DElncRNA-miRNA-DEmRNA interaction networks. In total, 197 DEcircRNAs, 685 DElncRNAs and 356 DEmRNAs were identified in prefrontal cortical tissues from Nrf2 (-/-) mice. The expression patterns of selected DEcircRNAs (except for mmu_circ_0003404) and DElncRNAs in qRT-PCR analyses were generally consistent with the microarray analysis results. Functional annotation of the DEmRNAs in the DEcircRNA/DElncRNA-miRNA-DEmRNA networks indicated that five non-coding RNAs (mmu_circ_0000233, ENSMUST00000204847, NONMMUT024778, NONMMUT132160 and NONMMUT132168) may contribute to Nrf2 activity, with the help of mmu_circ_0015035 and NONMMUT127961. The results also revealed that four non-coding RNAs (cicRNA.20127, mmu_circ_0012936, ENSMUST00000194077 and NONMMUT109267) may influence glutathione metabolism. Additionally, 44 DEcircRNAs and 7 DElncRNAs were found to possess coding potential. These findings provide clues to the molecular pathways through which Nrf2 protects neurons.

A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth.

OBJECTIVE: To evaluate the inhibitory role of a novel oncolytic adenovirus (OA), GP73-SphK1sR-Ad5, on the growth of hepatocellular carcinoma (HCC). METHODS: GP73-SphK1sR-Ad5 was constructed by integrating Golgi protein 73 (GP73) promoter and sphingosine kinase 1 (SphK1)-short hairpin RNA (shRNA) into adenovirus serotype 5 (Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1 (E1A) was detected by quantitative real-time PCR (qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK1sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). RESULTS: Transfection of GP73-SphK1sR-Ad5 significantly upregulated E1A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues. CONCLUSIONS: GP73-SphK1sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.

Differential Expression Profiles and Functional Prediction of Circular RNAs and Long Non-coding RNAs in the Hippocampus of Nrf2-Knockout Mice.

BACKGROUND: Nrf2 (nuclear factor, erythroid 2 like 2) is believed to play a major role in neurodegenerative diseases. The present study attempts to investigate the hippocampal circRNA and lncRNA expression profiles associated with Nrf2-mediated neuroprotection. METHODS: The hippocampal mRNA, circRNA and lncRNA expression profiles of Nrf2 (-/-) mice were determined by a microarray analysis. Bioinformatics analyses, including identification of differentially expressed mRNAs (DEmRNAs), circRNAs (DEcircRNAs) and lncRNAs (DElncRNAs), DEcircRNA-miRNA-DEmRNA interaction network construction, DElncRNA-DEmRNA co-expression network construction, and biological function annotation, were conducted. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the dysregulated expression of circRNAs and lncRNAs derived from the microarray data of the hippocampus of Nrf2 (-/-) mice. RESULTS: Compared to wild-type Nrf2 (+/+) mice, 412 DEmRNAs (109 up- and 303 down-regulated mRNAs), 1279 DEcircRNAs (632 up- and 647 down-regulated circRNAs), and 303 DElncRNAs (50 up- and 253 down-regulated lncRNAs) were identified in the hippocampus of Nrf2 (-/-) mice. Additionally, in the qRT-PCR validation results, the expression patterns of selected DEcircRNAs and DElncRNAs were generally consistent with results in the microarray data. The DEcircRNA-miRNA-DEmRNA interaction networks revealed that mmu_circRNA_44531, mmu_circRNA_34132, mmu_circRNA_000903, mmu_circRNA_018676, mmu_circRNA_45901, mmu_circRNA_33836, mmu_circRNA_ 34137, mmu_circRNA_34106, mmu_circRNA_008691, and mmu_circRNA_003237 were predicted to compete with 47, 54, 45, 57, 63, 81, 121, 85, 181, and 43 DEmRNAs, respectively. ENSMUST00000125413, NR_028123, uc008nfy.1, AK076764, AK142725, AK080547, and AK035903 were co-expressed with 178, 89, 149, 179, 142, 55, and 112 DEmRNAs in the Nrf2 (-/-) hippocampus, respectively. CONCLUSION: Our study might contribute to exploring the key circRNAs and lncRNAs associated with Nrf2-mediated neuroprotection.

Proteinase-activated receptor 2 promotes tumor cell proliferation and metastasis by inducing epithelial-mesenchymal transition and predicts poor prognosis in hepatocellular carcinoma.

AIM: To clarify the role of proteinase-activated receptor 2 (PAR2) in hepatocellular carcinoma, especially in the process of metastasis. METHODS: PAR2 expression levels were assessed by qRT-PCR and immunohistochemistry (IHC) in patient tissues and in hepatocellular carcinoma cell lines SMMC-7721 and HepG2. Cell proliferation and metastasis were assessed both in vitro and in vitro. Immunoblotting was carried out to monitor the levels of mitogen-activated protein kinase (MAPK) and epithelial-mesenchymal transition markers. RESULTS: The prognosis was significantly poorer in patients with high PAR2 levels than in those with low PAR2 levels. Patients with high PAR2 levels had advanced tumor stage (P = 0.001, chi-square test), larger tumor size (P = 0.032, chi-square test), and high microvascular invasion rate (P = 0.037, chi-square test). The proliferation and metastasis ability of SMMC-7721 and HepG2 cells was increased after PAR2 overexpression, while knockdown of PAR2 decreased the proliferation and metastasis ability of SMMC-7721 and HepG2 cells. Knockdown of PAR2 also inhibited hepatocellular carcinoma tumor cell growth and liver metastasis in nude mice. Mechanistically, PAR2 increased the proliferation ability of SMMC-7721 and HepG2 cells via ERK activation. Activated ERK further promoted the epithelial-mesenchymal transition of these cells, which endowed them with enhanced migration and invasion ability. CONCLUSION: These data suggest that PAR2 plays an important role in the proliferation and metastasis of hepatocellular carcinoma. Therefore, targeting PAR2 may present a favorable target for treatment of this malignancy.

[Ecological risk assessment and its management of Bailongjiang watershed, southern Gansu based on landscape pattern].

Watershed ecological risk assessment is an important research subject of watershed ecological protection and environmental management. Research on the ecological risk focuses on addressing the influence of human activities and its spatial variation at watershed scale is vital to policy-making to control the impact of human activity and protocols for sustainable economic and societal development. A comprehensive ecological environment index, incorporating a landscape index and an assessment of ecological vulnerability, was put forward to assess the spatio-temporal characteristics of ecological risk of the Bailongjiang watershed, southern Gansu Province, Northwest China. Using ArcGIS and Fragstats software and a land use map of 2010, an ecological risk map was obtained through spatial sampling and disjunctive Kriging interpolation. The results indicated that there were some obvious spatial differences of ecological risk levels in the watershed. The ecological risk level of the north and northwest of the Bailongjiang was higher than that of the western and southern extremities of the watershed. Ecological risk index (ERI) of Wudu and Tanchang was higher than that of Wenxian and Diebu. Some measures for ecological risk management were put forward on the basis of ERI of Bailongjiang watershed. To strengthen the integrated management of human activities and land use in the watershed, to carry out the vegetation restoration and ecological reconstruction, and to reduce the ecological risks and hazards of irrational human disturbance, are vital to the realization 'multiple-win' of the economic, social and ecological protection and for the sustainable development in the hilly area in southern Gansu.

Analysis of the causes and clinical characteristics of jejunoileal hemorrhage in China: a multicenter 10 year retrospective survey.

BACKGROUND: A retrospective study was performed to assess the causes, diagnostic methods for, and clinical features of, jejunoileal hemorrhage in Shandong province, China and to derive recommendations for management of this condition from these data. METHODS: We performed a retrospective systematic collection of data from between January 1999 and December 2008 in seven cities in Shandong province, China, identified 72 patients with jejunoileal hemorrhage and analyzed the relevant clinical data. RESULTS: Overall, tumors were the most common cause of jejunoileal hemorrhage (42 patients, 58.3%). The causes of this condition were significantly different (P < 0.05) in male and female patients. In male patients, the commonest factors were tumor (52.2%), enteritis (17.4%) and angiopathy (15.2%). However, in female patients, tumors accounted for a greater proportion of cases (18/26, 69.2%). In 38 cases (52.8%) the diagnosis was made by intraoperative enteroscopy or laparotomy, in 14 by capsule endoscopy and in the remainder by radiological methods. The most frequent presentation was melena (62.7%), followed by maroon stools (26.9%) and hematochezia (9.0%). Of the 72 patients,laparotomy is the main treatment method. CONCLUSION: Tumor, enteritis and angiopathy and diverticular disease are the most common causes of jejunoileal hemorrhage in Shandong province, China. The main clinical manifestations are bloody stools, most commonly in the form of melena, with or without abdominal pain. We recommend that female patients over the age of 40 with jejunoileal hemorrhage accompanied by abdominal pain should undergo urgent further assessment because of the strong probability of jejunoileal tumor.

[Relationship between the expression of human leukocyte antigen-b in peripheral blood leukocytes and the differentiation and metastasis of gastric carcinoma].

OBJECTIVE: To investigate the relationship between the expression of host human leukocyte antigen-B mRNA (HLA-B mRNA) and HLA-B antigen in peripheral blood leukocytes (PBLs) and the differentiation and metastasis of gastric carcinoma (GC). METHODS: To design and screen specific primers of HLA-B gene independently, detect the expression of HLA-B mRNA from 30 GC patients by reverse transcription-PCR and compare with the HLA-B antigen expression measured by flow cytometry. RESULTS: The expression rate of PBL HLA-B mRNA from GC patients (23. 3% ) was very significantly lower than that of normals (87. 5% ) (P <0. 01) , especially concerning the poorly differentiated GC patients with lymph node metastasis (16. 0% ). Measured by flow cytometry, the expression percentage of HLA-B antigen of well-differentiated GC patients without lymph node metastasis was 88. 2% , an obviously decreasing tendency was showed in comparison with that in the normal group (98. 8% ) , although the difference was not significant (P = 0. 056) , and the expression percentage in poorly differentiated GC patients with lymph node metastasis(73. 3% )was declined significantly (P <0. 05). CONCLUSION: The expression of PBL HLA-B mRNA and HLA-B antigen in GC patients is decreased or lost, and correlated with differentiation and metastasis of the cancer. The expression of PBL HLA-B mRNA may more directly reflect its relationship with the tumor differentiation and metastasis than that of HLA-B antigen.

Analysis of clinical features of acute pancreatitis in Shandong Province, China.

AIM: To investigate and obtain a more comprehensive view of the etiology and clinical features of acute pancreatitis in China. METHOD: The study comprised 1471 patients in 10 cites of China who were admitted to hospitals for acute pancreatitis from January 1992 to December 2002. Data for each patient were collected on a standardized form. RESULTS: Of the 1471 patients (854 men, 617 women; mean age 43.3 years; range 13-82 years), 1280 had mild pancreatitis and 191 had the severe form. Cholelithiasis (20.2%), alcohol (17.3%) and diet-induced (12.4%) were the most frequent etiological factors, followed by biliary tract infections (5.6%), hyperlipidemia (2.3%) and other factors (5.1%). However, in about 36.1% of cases, the etiology of acute pancreatitis still remained unexplained. In coastal regions, cholelithiasis was the most frequent factor but alcohol ranked first in interior regions. In males, a small predominance of alcohol over cholelithiasis was seen (27.4%vs 14.3%) and there was a clear predominance of cholelithiasis over alcohol (28.4%vs 3.2%) in females. The differences in the frequency of cholelithiasis and alcohol between coastal regions and interior regions and males and females were statistically significant (P < 0.01). According to their frequency, complications of acute pancreatitis were pancreatic pseudocyst, pancreatic ascites and bacterial peritonitis, pulmonary infections, multiple organ failure, diabetes mellitus type 2 and shock. CONCLUSION: Cholelithiasis, alcohol and diet-induced factors were the main etiological factors seen in China, whereas cholelithiasis alone predominated in females and alcohol ranked first in males. In about 36.1% of cases, the etiology of acute pancreatitis remained unknown. More attention should be paid to studying the etiologies of acute pancreatitis that remain unknown.

Analysis of the clinical features of recurrent acute pancreatitis in China.

BACKGROUND: Since few systematic studies have focused on recurrent acute pancreatitis in China, we sought to investigate its clinical features, including etiological factors and relative frequency. METHODS: Patients were selected from a total 1471 patients with acute pancreatitis in ten cities of China. All had been admitted to a hospital with an attack of acute pancreatitis between January 1992 and December 2002. Data for each patient was recorded on a standardized form. RESULTS: Of the 1471 patients with acute pancreatitis, 157 (10.7%) had recurrent acute pancreatitis. The majority (63%) were male, with a mean age of 41 years (range, 13-82 years). Regarding the etiology, alcohol (20.4%) and cholelithiasis (20.4%) were the most frequent causes, followed by diet (13.4%), hypertriglyceridemia (8.3%), biliary tract infection (5.7%), other (5.1%), and idiopathic factors (26.8%). Alcohol was most frequent in male patients (30.3%), whereas cholelithiasis was most frequent (34.5%) in female patients. The majority of patients (79.6%) presented with their second attack of pancreatitis. Complications of recurrent acute pancreatitis in order of frequency were pancreatic pseudocyst, multiple organ failure, diabetes mellitus type 2, and shock. CONCLUSIONS: Recurrent acute pancreatitis remains a frequent disease, with cholelithiasis and alcohol being the most usual etiological factors. Alcohol is the primary etiological factor in male patients. In about 26.8% of cases, the etiology remains unknown.

[The clinical features of acute pancreatitis in 10 cities in Shandong Province].

OBJECTIVE: To investigate and obtain a more comprehensive view of the etiology and clinical features of acute pancreatitis (AP) in Shandong Province. METHODS: 1471 cases admitted to hospital for AP were studied and collected from the ten cities of Shandong Province from January 1992 to December 2002 retrospectively. Data of each enrolled patient was recorded in a standardized form. RESULTS: In the 1471 patients, the ratio of male: female was 854:617, and also the mean age of them and the range was 43.3 and from 13 - 82 years old. 1280 had mild AP, and 191 had sever AP. Cholelithiasis (20.2%), alcohol (17.3%) and diet-induced (12.4%) were the most frequent etiologic factors, followed by biliary tract infections (5.6%), hyperlipemia (2.3%), other factors (5.1%). But in about 36.1% cases, the etiology of AP still remains unexplained. In coastal regions, cholelithiasis is the most frequent factor but in interior regions alcohol ranked first. In male, a small predominance of alcohol over cholelithiasis was seen (27.4 vs.14.3%, P < 0.01); and in female, there was a clear predominance of cholelithiasis over alcohol (28.4 vs. 3.2%, P < 0.01). The complications of AP were pancreatic pseudocyst, ascites and peritonitis, pulmonary infections, multiple organ failure, diabetes mellitus-2 and shock, etc. according to their frequencies. CONCLUSIONS: Cholelithiasis, alcohol and diet-induced factor were main etiologic factors in Shandong Province, whereas cholelithiasis alone predominated in the females. In about 36.1% cases, the etiology remains unknown. So that more attention should be paid to study the etiology of AP.