Primary Intrahepatic Mesothelioma: Case Series and Systematic Review of Literature.

BACKGROUND: Primary intrahepatic mesothelioma (PIHMM) has been rarely reported. Its typical clinical presentation, radiological features and pathology have not been defined. Here, we aimed to summarize its diagnosis and treatment. METHODS: We conducted a retrospective analysis of three cases of PIHMM in the First Affiliated Hospital of Zhejiang University School of Medicine and reviewed the current literature to investigate the clinical and pathological characteristics and prognosis of PIHMM. RESULTS: Based on our case series and the literature, the mean age of PIHMM was 59.7 (41-83) years. Most patients present with nonspecific symptoms such as abdominal pain, fever, weight loss and weakness. On imaging, PIHMM usually presented as a solid, heterogeneous soft tissue mass with irregular margins and significant enhancement of the margins in the arterial phase. Immunohistochemical markers such as calretinin, cytokeratin (CK)5/6, D2-40, WT-1, mesothelin CK and vimentin may be useful for diagnosis. The 3-year relapse-free survival rate (RFS) was 51.85%, the 3-year overall survival (OS) rate was 83.33% and the 3-year postoperative overall survival rate was 100%. CONCLUSION: PIHMM can only be diagnosed by careful postoperative pathology, because of its nonspecific clinical presentations, serological indicators or imaging features. Immunohistochemical staining is very useful to distinguish this tumor from other liver tumors. Surgery is the mainstay of treatment.

Pathological complete response after conversion therapy in unresectable hepatocellular carcinoma: a retrospective study.

BACKGROUND: Hepatocellular carcinoma is a highly lethal tumor worldwide, and China has a correspondingly high incidence and mortality rate. For patients with unresectable hepatocellular carcinoma, the prognosis is often poor. The objective of this retrospective study was to investigate the effects of conversion therapies on these patients. METHODS: The study included patients between the ages of 18 and 75 who were initially diagnosed with unresectable hepatocellular carcinoma and received conversion therapy. After completing surgery, the patients underwent pathological diagnosis, which showed complete necrosis. The study was conducted retrospectively at the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2019 to December 2021. The main objectives of the study were to evaluate the overall survival and recurrence-free survival. RESULTS: A total of 60 patients who met the inclusion criteria were enrolled. The median age of the patients was 56.6 ± 9.5 years, and 85% of them were male. The one-year overall survival rate (OS) was 98.3%, and the three-year OS was 95.6%. The one-year recurrence-free survival rate (RFS) was 81.1%, and the three-year RFS was 71.4%. In subgroup analysis, there was no statistically significant difference in RFS between patients with BCLC stages 0-A and BCLC stages B-C (p = 0.296). Additionally, there was no statistically significant difference in RFS between patients who received postoperative new adjuvant therapy and those who did not (p = 0.324). CONCLUSIONS: Conversion therapy followed by surgical resection could be a promising treatment for patients with initially unresectable hepatocellular carcinoma, and the prognosis is good with a pathological complete response.

Hemorrhagic Shock Sensitized the Diaphragm to Ventilator-Induced Dysfunction through the Activation of IL-6/JAK/STAT Signaling-Mediated Autophagy in Rats.

Mechanical ventilation (MV) is a major life support technique for the management of trauma-associated hemorrhagic shock (HS). Ventilator-induced diaphragm dysfunction (VIDD), one of the most common complications of MV, has been well demonstrated in animal and human studies. However, few data are available concerning the effects of MV on diaphragm function in HS victims. In the present study, we found diaphragm muscle atrophy and weakness in HS but not in healthy animals after 4 hours of MV. The inhibition of autophagy resulted in reduced muscle fiber atrophy and improved forces. In addition, we observed diaphragmatic interleukin- (IL-) 6 overexpression and activation of its downstream signaling JAK/STAT in HS animals after MV, and either the neutralization of IL-6 or the inhibition of the JAK/STAT pathway attenuated autophagy, diaphragm atrophy, and weakness. Importantly, treatment with nonselective antioxidant exerted no protective effects against VIDD in HS animals. In addition, in vitro study showed that exogenous IL-6 was able to induce activation of JAK/STAT signaling and to increase autophagy in C2C12 cells. Moreover, the inhibition of JAK/STAT signaling abolished IL-6-induced cell autophagy. Together, our results suggested that HS sensitized the diaphragm to ventilator-induced atrophy and weakness through the activation of IL-6/JAK/STAT signaling-mediated autophagy in rats.

Preoperative risk stratification for early recurrence of HBV-related hepatocellular carcinoma after deceased donor liver transplantation: a five-eight model development and validation.

BACKGROUND: Early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is associated with poor surgical outcomes. This study aims to construct a preoperative model to predict individual risk of post-LT HCC recurrence. METHODS: Data of 748 adult patients who underwent deceased donor LT for HCC between January 2015, and February 2019 were collected retrospectively from the China Liver Transplant Registry database and randomly divided into training (n = 486) and validation(n = 262) cohorts. A multivariate analysis was performed and the five-eight model was developed. RESULTS: A total of 748 patients were included in the study; of them, 96% had hepatitis B virus (HBV) and 84% had cirrhosis. Pre-LT serum alpha-fetoprotein (AFP), tumor number and largest tumor diameter were incorporated to construct the 5-8 model which can stratify patients accurately according to their risk of recurrence into three prognostic subgroups; low-(0-5 points), medium-(6-8 points) and high-risk (> 8 points) with 2-year post-LT recurrence rate of (5,20 and 51%,p <  0.001) respectively. The 5-8 model was better than Milan, Hangzhou, and AFP-model for prediction of HCC early recurrence. These findings were confirmed by the results of the validation cohort. CONCLUSIONS: The 5-8 model is a simple validated and accurate tool for preoperative stratification of early recurrence of HCC after LT.

[Habitat suitability evaluation for Angelica dahurica planting in Yanting county,Sichuan province based on GIS].

It is of great significance to analyze habitable suitability of genuine medicinal materials for Chinese herbal medicine planting according to local environment,for medicinal resources protecting and for reasonable planning introduction. Based on GIS technology,the analytic hierarchy process was applied to analyze the spatial differentiation of habitat suitability of Angelica dahurica in Yanting county of Sichuan province. The evaluation combined local geographical environment characteristics and habitat requirements for A. dahurica planting and adopted the expert experience method to screen out the evaluation index for establishing evaluation system.With the established evaluation system,the index weight of evaluating index was determined by analytic hierarchy process and their grouping values were assigned by Delphi method. The all evaluating index were translated into index distribution maps using Arc GIS software. Using the comprehensive factor weighted evaluating model and spatial index distribution map,the evaluation was obtained by means of the overlay analysis function of Arc GIS 10. 3 software. RESULTS:: showed that A. dahurica had a wide range of suitable planting areas in Yanting county. Highly suitable areas amounted to 165. 01 km2,and mainly distributed in the low hilly area with moderate elevation and fertile soil. Moderately suitable areas amounted to 798. 92 km2 which had extensive distribution in middle and west part of the county. Marginally suitable areas amounted to 0. 33 km2,where the soil was highly viscous with high altitude and low temperature that was not conducive to the growth and development of A. dahurica. Adapting to local conditions and scientific planning plays an important role in the development of local characteristic planting industry of genuine medicinal materials.

Prediction of Early Recurrence of Hepatocellular Carcinoma in Patients with Cirrhosis Who Had Received Deceased Donor Liver Transplantation: A Multicenter Study.

BACKGROUND Early recurrence after liver transplantation (LT) is still a clinical problem. This multicenter study evaluated the Milan, Hangzhou, and AFP model-based criteria for prediction of early recurrence of HCC in patients with cirrhosis who had undergone LT. MATERIAL AND METHODS From the China Liver Transplant Registry (CLTR) database, we analyzed data of 589 HCC patients who had undergone LT between Jan 2015 and Jan 2019. Imaging data and AFP levels were evaluated immediately before LT. Recurrence and overall survival rates at 2 years were tested using the Kaplan-Meier estimate. The Milan criteria, Hangzhou criteria, and AFP model-based criteria were evaluated. RESULTS We found that 62.0%, 91.2%, and 67.6% of patients were within the Milan criteria, Hangzhou criteria, and AFP model-based criteria, respectively. The 2-year recurrence rate was 8.9%, 15.8%, and 11.8% with corresponding overall survival of 85.3%, 82.7%, and 86.5%, respectively. The 2-year recurrence rate was different in patients fulfilling and exceeding the AFP model-based criteria among patients who met either the Milan criteria (7.9% vs. 18.8%, HR=3.83, p=0.006) or Hangzhou criteria (12.0% vs. 27.6%, HR=2.95, p<0.001). However, the 2-year recurrence rate was not significantly different among patients who were beyond either the Milan or Hangzhou criteria. CONCLUSIONS For the prediction of early recurrence of HCC in patients with cirrhosis after liver transplantation, Milan criteria, Hangzhou criteria, and AFP model-based criteria are effective predictive tools for stratification of patients into low- and high-risk groups of recurrence with different prognoses. The AFP model-based criteria can identify a subgroup of patients with high risk of recurrence among patients who met either Milan or Hangzhou criteria.

Fluid resuscitation with preventive peritoneal dialysis attenuates crush injury-related acute kidney injury and improves survival outcome.

BACKGROUND: In-hospital renal replacement therapy (RRT) is widely used for the treatments of acute kidney injury (AKI) in crush injury (CI) victims. This study was designed to investigate whether preventive peritoneal dialysis (PPD) is useful for renal protection in CI. METHODS: Animals received hindlimb compressions for 6 h to induce CI. Then, animals were untreated or treated with PPD and/or massive fluid resuscitation (MFR) for 8 h since the onset of compression release. Blood and renal tissue samples were collected at various time points for biological and morphological analysis. RESULTS: PPD attenuated lactic acidosis and reduced serum K+ and myoglobin levels in CI animals. In addition, PPD was effective in removing blood urea nitrogen (BUN) and creatinine, and reduced renal expressions of neutrophil gelatinase-associated lipocalin (NGAL). The combination of PPD and MFR furtherly attenuated AKI with significantly decreased histological scores (p = 0.037) and reduced NGAL expressions (p = 0.0002) as compared with the MFR group. Moreover, MFR + PPD group had a significantly higher survival rate than that in the MFR and the PPD groups (p < 0.05, respectively). CONCLUSION: The use of PPD at the onset of compression release is beneficial for renal protection and survival outcome in a rabbit model of CI.

Renoprotective effects of brown adipose tissue activation in diabetic mice.

BACKGROUND: Brown adipose tissue (BAT) has been regarded as a potential target organ to combat obesity and related metabolic disorders. However, the effect of BAT activation on the development of diabetic kidney disease (DKD) remains unclear. METHODS: Diabetic mice were induced by streptozotocin (STZ) combined with a high-fat diet. To activate BAT, mice were administered 1 mg/kg per day, i.p., CL316,243, a ß3 -adrenergic receptor agonist, for 4 weeks. Blood glucose, serum lipids, adipokines, 24-hour urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG), and circulating microRNA (miRNA) levels were analyzed, in addition to renal pathology. Histological changes (fibrosis, inflammation) were evaluated in the kidneys, as was the expression of oxidative stress-related genes. Renal signaling pathways (fibroblast growth factor [Fgf]21/ß-klotho/FGF receptor 1c and AMP-activated protein kinase[AMPK]/sirtuin 1 [Sirt1]/peroxisome proliferator-activated receptor-γ coactivator-1α [Pgc1α]) were also evaluated. RESULTS: Compared with untreated STZ-diabetic mice, CL316,243 treatment reduced blood glucose, albeit not significantly (20.58 ± 3.55 vs 23.60 ± 3.90 mM), and significantly decreased triglycerides and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Simultaneously, BAT activation significantly decreased 24-hour urinary albumin (34.21 ± 6.28 vs 70.46 ± 15.81 µg/24 h; P < 0.05) and 8-OHdG, improved renal fibrosis, inflammation, and oxidative stress, and ameliorated renal morphological abnormalities. In addition to enhancing BAT activity, CL316,243 significantly increased serum adiponectin concentrations and renal Fgf21 sensitivity, and reactivated the renal AMPK/Sirt1/Pgc1α signaling pathway. Furthermore, CL316,243 treatment increased levels of some circulating miRNAs and downregulated expression of their target genes in the kidney. CONCLUSIONS: Activating BAT could improve kidney injury in diabetic mice via metabolic improvements and renal AMPK activation by beneficial adipokines and miRNAs.