Search

Shuai Zhou, Chao Zhu, Shi Lei Chen, Jin Ang Li, Kang Lin Qu, Hao Jing, Yong Wang, Qing Pang, Hui Chun Liu Department of Hepatobiliary Pancreatic Surgery, Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Bengbu Medical College, Anhui, 233000, People’s Republic of ChinaCorrespondence: Hui Chun Liu; Qing PangDepartment of Hepatobiliary Pancreatic Surgery, Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Bengbu Medical College, Anhui, 233000, People’s Republic of ChinaEmail liuhcdoctor@126.com; portxiu2@126.comBackground: Pancreatic cancer is an aggressive malignant tumor of the digestive system and the fourth leading cause of tumor-related death. Intracavitary 125I seed irradiation has been recently developed as a therapy for locally advanced pancreatic head carcinoma. However, there are still many limitations, and more investigations are needed in order to optimize this new treatment method.Methods: Sixty-seven patients were included in our study; 41 cases treated by SEMS-CL-125I intracavular irradiation (SEMS-CL-125I group) and 26 cases treated by SEMS-CL-125I intracavular irradiation combined with 125I particle implantation in the tumor body (the combined group). Among the 67 patients, 43 were males and 24 were females, with an average age of 69.64± 8.84 years. Tumor site size was determined based on the MRI or CT imaging scans, and the number and radius of 125I particle placement were calculated according to a specific formula. 125I particles were inserted into the tumor with a radius of 1.5 cm and a row spacing of 1 cm. The main postoperative biochemical indexes, imaging analysis, postoperative analgesia degree, median survival time and rate of complications were compared between the two groups.Results: Jaundice and liver function improved in both groups after treatment for 6 months. The combined group did better. Kaplan–Meier analysis showed that patients in the combined group had a significantly better overall survival than those in the SEMS-CL-125I group. Patients in the combined group had less complications than those in the SEMS-CL-125I group (23.1% vs 34.1%), and the postoperative pain status of the combined group was improved (26.8% vs 53.8%).Conclusion: Compared with the SEMS-CL-125I intracavular irradiation alone, the combination of 125I seed implantation with solid tumor 125I seed implantation had a better therapeutic effect in LAPHC patients, with improved biochemical indicators, survival prognosis, pain relief, and fewer complications.Keywords: locally advanced pancreatic cancer, 125I, metal biliary stent

Serotonin exerts important functions in several liver pathophysiological processes. In this study, we investigated the role of serotonin in concanavalin A (Con A)-induced liver fibrosis (LF) in mice and the underlying mechanisms. To establish the mouse model of LF, mice of wild-type (WT) and tryptophan hydroxylase 1 (Tph1) knockout (serotonin depletion) received Con A for 8 successive weeks. Degree of fibrosis was assessed by Sirius red staining, as well as the measurements of alpha smooth muscle actin (α- SMA), hydroxyproline (Hyp) and type I collagen in liver tissues. To elucidate the potential mechanisms, we assessed the effect of serotonin depletion on inflammatory, oxidative stress as well as TGF-β1/Smads signaling pathway. We found that serotonin depletion significantly inhibited collagen deposition as evaluated by less collagenous fiber in Sirus Red staining and reduced contents of Hyp and type I collagen. In addition, the absence of serotonin significantly inhibited the release of several inflammatory cytokines, including interleukin-6 (IL-6), interferon-gamma (IFN-γ), tumor necrosis-alpha (TNF-α), and transforming growth factor β1 (TGF-β1). Oxidative stress was also largely mitigated in LF mice with serotonin deficiency as manifested by the decreases of oxidative stress markers (malonaldehyde (MDA) and myeloperoxidase (MPO)), as well as the increases of antioxidant stress indicators (glutathione (GSH), and GSH-px, catalase (CAT), superoxide dismutase (SOD)) in liver tissues. Moreover, the lack of serotonin may provide an antifibrotic role by inhibiting the intrahepatic expressions of TGF-β1, phosphorylated-smad2 (p-smad2), and phosphorylated-smad3 (p-smad3). These results indicated that, serotonin depletion attenuates Con A-induced LF through the regulation of inflammatory response, oxidative stress injury, and TGF-β1/Smads signaling pathway.

Background Platelet-albumin-bilirubin (PALBI) has been demonstrated to be superior to conventional Child-Pugh (C-P) grade in evaluating liver function and prognosis of HCC patients. However, both thrombocytosis and thrombocytopenia are unfavorable for HCC survival. The aim of this study was to preliminarily investigate the prognostic value of PALBI in HCC patients with thrombocytopenia and excluding thrombocytopenia. Methods In this retrospective cohort study, we reviewed 465 cases of HCC patients who underwent radical surgery. PALBI grade was calculated based on preoperative serological examinations. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS), which were assessed by Kaplan-Meier method and Cox regression. The prognostic performances of PALBI and other models were estimated by using the concordance index (C-index). Results During a median follow-up time of 28 months, 31.6% (147/465) of patients died and 33.5% (156/465) experienced recurrence. Multivariate analyses revealed that both thrombocytosis and thrombocytopenia were independently associated with poor OS and RFS compared with normal platelet count (PLT) in HCC patients. Stratified analysis further revealed that PALBI was a significant predictor for HCC survival in patients excluding thrombocytopenia but not in patients with thrombocytopenia. In particular, in HCC patients excluding thrombocytopenia, the combination of tumor size with PALBI (C-index = 0.730, 95% CI: 0.674-0.786) may be superior to the classical Barcelona Clinic Liver Cancer (BCLC) and Cancer of Liver Italian Program (CLIP) staging systems in predicting survival. Conclusion In conclusion, PALBI grade, in particular the combination with tumor size, is an effective model for discriminating survival in HCC patients excluding thrombocytopenia but not in thrombocytopenic HCC patients.

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Inflammatory bowel disease (IBD) is a persistent and chronic disease that is characterized by destructive gastrointestinal (GI) inflammation. Researchers are trying to identify and develop new and more effective treatments with no side effects. Acute and chronic mouse models of IBD were established using dextran sulfate sodium (DSS) solution. To evaluate the efficacy and mechanism, umbilical cord mesenchymal stem cells (UCMSCs) were obtained from Kunming (KM) mice and humans. In the chronic IBD study, the survival rates of the normal control, model, mouse UCMSC (mUCMSC) and human UCMSC (hUCMSC) groups were 100%, 40%, 86.7%, and 100%, respectively. The histopathological scores of the normal control, intraperitoneal injection, intravenous treatment, and model groups were 0.5 ± 0.30, 5.9 ± 1.10, 8.7 ± 1.39, and 8.8 ± 1.33 (p = 0.021). UCMSCs promoted the expression of the intestinal tight junction protein occludin, downregulated the protein expression of the autophagy marker LC3A/B in colon tissue, and upregulated the expression of VEGF-A and VEGFR-1 at the injured site. This study provides an experimental model for elucidating the therapeutic effects of UCMSCs in IBD. We provide a theoretical basis and method for the clinical treatment of IBD using UCMSCs.

Posthepatectomy liver failure (PHLF) is a life-threatening complication after liver resection, resulting in an increased morbidity and mortality. Epidemiological evidence of the association between preoperative albumin-bilirubin (ALBI) score, a newly established model for assessing liver functional reserve, and the risk of PHLF and mortality remains controversial. A systematical search for relevant literature was performed in PubMed, Embase, and Web of Science databases from December 2014 to September 2020. Odds ratio (OR) value and 95% confidence interval (CI) were extracted or calculated to synthetically estimate the association of preoperative ALBI score with PHLF and mortality. Meta-analyses were performed using a random-effects model. Twelve studies with a total of 21,348 patients were included in this meta-analysis. It was indicated that, compared to patients with a lower preoperative ALBI grade, patients with a higher grade had a significantly elevated risk of PHLF (6 studies, 18,291 patients; OR = 2.48, 95%CI: 2.00–3.07) and mortality (4 studies15, 139 patients; OR = 2.35, 95% CI: 1.38–4.00). In addition, when it was expressed as a continuous variable, ALBI was also a significant predictor of PHLF (6 studies, 3,833 patients; OR = 3.16, 95% CI: 2.07–4.81, per 1-point increase in ALBI score). No significant publication biases were detected as suggested by funnel plots inspection and Begg’s tests. The current meta-analysis demonstrates that preoperative elevated ALBI is associated with higher risk of PHLF and mortality after hepatectomy.

Background There is increasing evidence supporting coronavirus disease 2019 (COVID-19)-related coagulopathy. In the available literature, only 2 cases of superior mesenteric vein thrombosis have been described. Methods We present a peculiar case of high-grade small bowel obstruction in a patient with COVID-19 infection. Results Exploratory laparotomy revealed a congenital adhesion band with associated focal bowel ischemia contributed by superior mesenteric vein thrombosis and positive lupus anticoagulant. Conclusions It is important to consider the rare differential of mesenteric vein thrombosis and its related sequelae of mesenteric ischemia in a patient with COVID-19 who presents with abdominal pain.

To compare the efficacy and outcomes of self-expandable metallic stent combined with catheter-loaded iodine-125 seeds (SEMS-CL-125I) brachytherapy versus conventional palliative surgery (PS) in advanced extrahepatic cholangiocarcinoma (EHCC). The retrospective analysis consisted of 101 advanced EHCC patients who received SEMS-CL-125I (n = 67) or underwent PS (n = 34). The clinical characteristics, postoperative complications and overall survival (OS) were compared between the two groups. Serum levels of bilirubin, transaminase, and albumin (ALB) were significantly improved at 1 month, 3 months, and 6 months postoperatively in both groups (all P

As highly conserved non-coding RNAs of approximately 18–24 nucleotides, microRNAs (miRNAs) regulate the expression of target genes. Multiple studies have demonstrated that miRNAs participate in the regulation of human cancer. MircoRNA-217 (miR-217) participates in the regulation of various tumors by specifically binding target genes and post-transcriptional regulation. In recent years, there have been numerous reports about miR-217 in tumor progression. MiR-217 is known mainly as a tumor suppressor, although some studies have shown that it functions as an oncomiR. Here, we review the current research related to miR-217, including its role in tumor progression and the molecular mechanisms.

Phosphoglucomutase (PGM) is a key enzyme in glycolysis and gluconeogenesis, regulating both glycogen and trehalose metabolism in insects. In this study, we explored the potential function of phosphoglucomutase (PGM) using RNA interference technology in Nilaparvata lugens, the brown planthopper. PGM1 and PGM2 were found highly expressed in the midgut of brown planthoppers, with different expression levels in different instar nymphs. The glycogen, glucose, and trehalose levels were also significantly increased after brown planthoppers were injected with dsRNA targeting PGM1 (dsPGM1) or PGM2 (dsPGM2). In addition, injection of dsPGM1 or dsPGM2 resulted in increased membrane-bound trehalase activity but not soluble trehalase activity. Furthermore, the expression of genes related to trehalose and glycogen metabolism decreased significantly after injection with dsPGM1 and dsPGM2. The expression levels of genes involved in chitin metabolism in the brown planthopper were also significantly decreased and the insects showed wing deformities and difficulty molting following RNAi. We suggest that silencing of PGM1 and PGM2 expression directly inhibits trehalose metabolism, leading to impaired chitin synthesis. Electronic supplementary material The online version of this article (10.1007/s13205-020-2053-5) contains supplementary material, which is available to authorized users.

Ischemia-reperfusion injury is an important contributor to acute kidney injury and a major factor affecting early functional recovery after kidney transplantation. We conducted this experiment to investigate the protective effect of induced multipotent stem cell transplantation on renal ischemia-reperfusion injury. Forty rabbits were divided into four groups of 10 rabbits each. Thirty rabbits were used to establish the renal ischemia-reperfusion injury model, and ten rabbits served as the model group and were not treated. Among the 30 rabbits with renal ischemia-reperfusion injury, 10 rabbits were treated with induced peripheral blood mononuclear cells (PBMCs), and 10 other rabbits were treated with noninduced PBMCs. After three weekly treatments, the serum creatinine levels, urea nitrogen levels and urine protein concentrations were quantified. The kidneys were stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome and then sent for commercial metabolomic testing. The kidneys of the rabbits in the model group showed different degrees of pathological changes, and the recovery of renal function was observed in the group treated with induced cells. The results indicate that PBMCs differentiate into multipotent stem cells after induction and exert a therapeutic effect on renal ischemia-reperfusion injury.

This study aimed at investigating the efficacy of percutaneous transhepatic biliary stenting (PTBS) combined with 125I seeds intracavitary irradiation in the treatment of extrahepatic cholangiocarcinoma (EHC) and to preliminarily explore the prognostic values of inflammation-based scores in these patients. A total of 113 clinically/pathologically diagnosed cases of EHC who received PTBS combined with 125I seeds implantation were retrospectively analyzed. The postoperative changes of clinical symptoms and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total serum bilirubin (TBIL), direct bilirubin (DBIL), and albumin (ALB) were observed. Preoperative clinical data were extracted to calculate inflammation-based scores, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelets-to-lymphocyte ratio (PLR). Kaplan–Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of inflammation-based scores. After operation, clinical symptoms such as jaundice and fever significantly improved in all patients. At 1 month and 3 months postoperatively, serum levels of ALT, AST, ALP, TBIL, and DBIL significantly reduced, and ALB significantly increased, compared with preoperative values. The median survival time of the patients was 12 months and the 1-year survival rate was 56.8%. Univariate analysis revealed that factors related to overall survival were CA19-9, TBIL, ALB, SII, and NLR. Multivariate analysis further identified SII and NLR as independent prognostic models. The combination of PTBS and 125I seeds intracavitary irradiation is an effective palliative treatment for advanced EHC. Elevated SII and NLR can be used to predict poor survival.

Background To date, epidemiological evidence of the association between preoperative prognostic nutritional index (PNI) and the prognosis of hepatocellular carcinoma (HCC) remains controversial. Methods A literature search was performed in the databases of PubMed, Embase, and Web of Science. Hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were extracted to estimate the association of preoperative PNI with overall survival (OS), disease-free survival (DFS), and postoperative recurrence of HCC, respectively. A random-effects model was used to calculate the pooled effect size. Results Thirteen studies with a total of 3,738 patients with HCC met inclusion criteria for this meta-analysis. It indicated that a lower level of preoperative PNI was a significant predictor of worse OS (HR = 1.82, 95%CI: 1.44-2.31) and DFS (HR = 1.49, 95% CI: 1.06-2.07). In addition, risk of postoperative recurrence was significantly higher in patients with a lower preoperative PNI (OR = 1.92, 95% CI: 1.33-2.76). Subgroup analysis based on therapeutic intent demonstrated a significant positive association between preoperative low PNI and worse OS for those patients undergoing surgical resection and for those undergoing TACE or non-surgical treatment. Conclusion The current meta-analysis demonstrates that preoperative PNI is a prognostic marker in HCC.

Umbilical cord mesenchymal stem cells (UC-MSCs) exert strong immunomodulatory effects and can repair organs. However, their roles in radiation injury remain unclear. We show that in tree shrews with acute radiation injury, injected UC-MSCs significantly improved survival rates, reduced lung inflammation and apoptosis, prevented pulmonary fibrotic processes, recovered hematopoiesis, and increased blood counts. A protein microarray analysis showed that serum levels of the anti-inflammatory cytokines IL-10 and IL-13 and the growth factors BMP-5, BMP-7, HGF, insulin, NT-4, VEGFR3, and SCF were significantly higher, while those of the inflammatory cytokines IL-2, TIMP-2, TNF-α, IFN-γ, IL-1ra, and IL-8 and the fibrosis-related factors PDGF-BB, PDGF-AA, TGF-β1, IGFBP-2, and IGFBP-4 were significantly lower in UC-MSC-injected animals. A transcriptome analysis of PBMCs showed that the mRNA expression of C1q was upregulated, while that of HLA-DP was downregulated after UC-MSC injection. These results confirm the immunohistochemistry results. eGFP-labeled UC-MSCs were traced in vivo and found in the heart, liver, spleen, lungs, kidneys, thymus, small intestine and bone marrow. Our findings suggest that UC-MSC transplantation may be a novel therapeutic approach for treating acute radiation injury.

BACKGROUND AND OBJECTIVE The objective of this study was to investigate the prognostic significance of several inflammation-based models in hepatitis B-associated hepatocellular carcinoma (HCC). PATIENTS AND METHODS We retrospectively reviewed 470 cases of hepatitis B-associated HCC. Preoperative data were collected to calculate the inflammation-based markers, including systemic immune-inflammation index (neutrophil×platelets/lymphocyte), platelets-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio (NLR). Overall survival and recurrence-free survival were estimated by the Kaplan-Meier method and Cox analysis. RESULTS During a median follow-up time of 29 months, 34.0% (160/470) of patients died and 36.0% (169/470) experienced recurrence. Compared with patients with lower scores of inflammation models, patients in the higher group had larger tumor diameter and higher risk of vascular invasion (both P

Qing Pang,1,* Hao Jin,1,* Kai Qu,2,* Zhongran Man,1 Yong Wang,1 Song Yang,1 Lei Zhou,1 Huichun Liu1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China *These authors contributed equally tothis work Background: Recent studies have showed that nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the risk of several types of cancer. However, epidemiological evidence of the association between NSAIDs intake and the risk of hepatocellular carcinoma (HCC) remains controversial. Methods: To assess the preventive benefit of NSAIDs in HCC, we simultaneously searched the databases of PubMed, EmBase, Web of Science, and Scopus and screened eligible publications. Results: A total of twelve articles (published from 2000 to 2017) from five countries were identified by retrieval. We observed a significantly lower risk of HCC incidence among users of NSAIDs than among those who did not use NSAIDs (pooled hazard ratio [HR] value =0.81, 95% confidence interval [CI]: 0.69–0.94). No evidence of publication bias was observed (Begg’s test, P=0.755; Egger’s test, P=0.564). However, when stratified according to the categories of NSAIDs, users of non-aspirin NSAIDs (HR =0.81, 95% CI: 0.70–0.94), but not aspirin (HR=0.77, 95% CI: 0.58–1.02), showed a statistically significant reduced HCC incidence. We also found that NSAIDs use significantly reduced the recurrent risk of HCC, with a HR value of 0.79 (95% CI: 0.75–0.84), whereas there was no statistically significant association between NSAIDs use and HCC mortality, with a HR value 0.65 (95% CI: 0.40–1.06). Conclusion: Taken together, our meta-analysis demonstrates that NSAIDs significantly reduce the incident and recurrent risk of HCC. Keywords: NSAIDs, aspirin, hepatocellular carcinoma, incidence, recurrence

Hao Jin,1–3 Geliang Xu,2 Qiang Zhang,3 Qing Pang,3 Meifang Fang3 1School of Medicine, Shandong University, Jinan, 2Department of Hepatic Surgery, Anhui Provincial Hospital, Hefei, 3Department of Hepatobiliary Surgery, The First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China Background: Synaptotagmin-7 (Syt-7) is a member of the synaptotagmin (Syt) family, which plays an important role in many physiological and pathological processes. However, to the best of our knowledge, there is no study describing its function in tumors, particularly in hepatocellular carcinoma (HCC). Therefore, in this study, we examined the role of Syt-7 in HCC and attempted to elucidate its underlying mechanism. Materials and methods: We examined the expression levels of Syt-7 in HCC cell lines and normal hepatocytes by real-time quantitative polymerase chain reaction analysis. The effects of Syt-7 knockdown on in vitro cell growth were assessed by Celigo image cytometry, MTT assay, colony formation assay, and cell cy cle analysis. In vivo tumorigenesis was evaluated using a nude mouse model. The underlying molecular mechanism was evaluated using a PathScan Stress Signaling Antibody Array. Results: Syt-7 mRNA levels were highly expressed in Huh-7 and Hep3B cells; moderately expressed in SMMC-7721, HepG2, and BEL-7402 cells; and lowly expressed in normal hepatocytes L-O2. Functional experiments demonstrated that Syt-7 knockdown significantly suppressed cell proliferation and induced cell cycle arrest by increasing phosphorylation of Chk1 and p53. Furthermore, Syt-7 knockdown remarkably reduced the growth of xenograft tumors in mice. Conclusion: The results of this study suggest that Syt-7 plays a vital role in tumorigenesis and in the development of HCC. Syt-7 can be used as a new diagnostic and therapeutic target in HCC. Keywords: hepatocellular carcinoma, Syt-7, Chk1, p53, cell cycle

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The aim of this study is to investigate the role of 5-HT on cecal ligation and puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The results showed that the 5-HT-sufficient group mice had a significantly lower survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group was higher than that in the WT-CLP sepsis group and was much closer to the normal body temperature 24 hours after CLP. The tissue histopathology analysis revealed that 5-HT markedly exacerbated histological damages in the peritoneum, lung, liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant lower levels of TNF-α, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis.

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3+ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 107/kg, which is 10 times of that in clinical human use.

We aimed to compare the efficacy of percutaneous transhepatic biliary stenting (PTBS) and PTBS combined with 125I particles implantation in the treatment of advanced extrahepatic cholangiocarcinoma (EHC). A total of 184 advanced EHC patients, who received PTBS (PTBS group) or PTBS combined with 125I particles implantation (PTBS + 125I group) from January 2012 to April 2017 in our department, were retrospectively reviewed. The improvement of jaundice and liver function was observed in both groups. The postoperative complications, risk of biliary re-obstruction, and overall survival (OS) were compared between the two groups. Amongst, 71 cases received PTBS and 113 had the additional implantation of 125I particles. The jaundice and liver function were significantly improved in all patients, especially in PTBS + 125I group. There was no significant difference in the risk of postoperative complications between the two groups. However, the risk of biliary re-obstruction significantly reduced in PTBS + 125I group (19.5% vs. 35.2%, p = 0.017). Kaplan Meier analysis showed that patients in PTBS + 125I group had a significantly better OS, both for hilar and distal cholangiocarcinoma. Univariate analysis demonstrated that preoperative levels of carbohydrate antigen 19-9 (CA19-9), total bilirubin, neutrophil count, lymphocyte count, and different therapeutic method were significant factors affecting OS. Multivariate analysis further identified the treatment of PTBS combined with 125I particles implantation as an independent protective prognostic factor (HR = 0.26, 95% CI: 0.17–0.39, p 125I particles implantation is superior to PTBS alone in improving liver function, inhibiting biliary re-obstruction, and prolonging survival time.

Background: Laparoscopic hepatectomy (LH) has been reported as a safe and efficacious treatment for hepatocellular carcinoma (HCC) patients. However, in cirrhosis patients, LH may be more ...

Ethnopharmacological relevance Monascus-fermented rice product (MFRP) has been regarded as a dietary supplement and traditional medicine with circulation-promoting effects in China and other countries for centuries. Aim of the study This study was carried out to profile the chemical components in MFRP, and provide available information for elucidating the potential lipid-lowering compounds other than monacolins. Materials and methods High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS) and gas chromatography coupled with mass spectrometry (GC-MS) methods were applied to comprehensive analysis of chemical components in MFRP. Potential small molecules were identified by comparing with reference standards, or tentatively characterized by comparing their retention time and high-resolution mass spectral data with previous literature. The lipid-lowering properties of ten major non-monacolin compounds were evaluated in cholesterol-fed zebrafish larvae. And one with optimum lipid-lowering activity was subsequently evaluated in high fat diet-fed C57BL/6 J mice, with the dyslipidemia and ectopic lipid deposition being investigated. Results A total of 99 compounds were characterized in MFRP, including 38 monacolins, 5 decalins, 6 isoflavones, 13 pigments, 8 azaphilonoids, 11 amino acids, 4 nucleosides, 9 lipid acids, 4 phytosterols and glycerol. The preliminary screening showed that ergosterol remarkably reduced cholesterol levels in zebrafish larvae. Moreover, ergosterol delayed body weight gain and decreased circulating total cholesterol, triglyceride, low density lipoprotein cholesterol levels in high fat diet-fed mice. Ectopic lipid accumulation was also ameliorated in the liver and heart of obese mice. Conclusion Global analysis of chemical components and screening of lipid-lowering non-monacolin compounds in MFRP have improved our understanding of its therapeutic material basis.

The pretreatment nutritional and immunological status play indispensable roles in predicting the outcome of patients with various types of malignancies. The aim of the study was to investigate whether preoperative prognostic nutritional index (PNI), which simply accounts for nutritional and immunological status, was associated with overall survival (OS) in patients with gallbladder carcinoma (GBC). The retrospective study included a total of 315 GBC patients after surgery between 2002 and 2012. PNI was calculated according to the following formula: 10× serum albumin (g/dl) +0.005× total lymphocyte count (per mm3). A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff value for LMR, which was set at 46.14. According the value, patients were categorized into two different groups, namely high-PNI group (n = 133) and low-PNI group (n = 182). The univariate and multivariate Cox regression models were used to identify the independent prognostic factors. The results showed that low pretreatment PNI value was significantly associated with elderly age, partial surgery procedure, and advanced tumor status such as tumor stage, node stage, and tumor-node-metastasis stage (P

The relationship between telomere length and cancer survival has been widely studied. To gain a deeper insight, we reviewed the published studies. A total of 29 studies evaluated telomere length in the peripheral blood; 22 studies evaluated telomere length in the tumor tissue. First, in the peripheral blood studies, for solid tumor patients with shortened telomere length, the combined hazard ratios (HRs) for mortality and tumor progression were 1.21 (95%CI, 1.10-1.32) and 1.71 (95%CI, 1.37-2.13), respectively. Meanwhile, in hematology malignancy, the combined HRs for mortality and tumor progression were 2.83 (95%CI, 2.14-3.74) and 2.65 (95%CI, 2.18-3.22), respectively. Second, in the studies that use tumor tissue, for patients with shortened telomeres, the combined HRs for mortality and tumor progression were 1.26 (95%CI, 0.95-1.66) and 1.65 (95%CI, 1.26-2.15), respectively. In the studies that calculate the telomere length ratios of tumor tissue to adjacent normal mucosa, for patients with lower telomere length ratios, the combined HRs were 0.66 (95%CI, 0.53-0.83) and 0.74 (95%CI, 0.41-1.32) for mortality and tumor progression, respectively. In conclusion, shortened telomere in peripheral blood and tumor tissue might indicate poor survival for cancer patients. However, by calculating the telomere length ratios of tumor tissue to adjacent normal mucosa, the lower ratio might indicate better survival.

Evidence is accumulating highlighting the importance of extracellular miRNA as a novel biomarker for diagnosing various kinds of malignancies. MiR-21 is one of the most studied miRNAs and is over-expressed in cancer tissues. To explore the clinical implications and secretory mechanisms of extracellular miR-21, we firstly meta-analyzed the diagnostic efficiency of extracellular miR-21 in different cancer types. Eighty-one studies based on 59 articles were finally included. In our study, extracellular miR-21 was observed to exhibit an outstanding diagnostic accuracy in detecting brain cancer (area under the summary receiver operating characteristic curve or AUC = 0.94), and this accuracy was more obvious in glioma diagnosis (AUC = 0.95). Our validation study (n = 45) further confirmed the diagnostic and prognostic role of miR-21 in cerebrospinal fluid (CSF) for glioma. These findings inspired us to explore the biological function of miR-21. We next conducted mechanistic investigations to explain the secretory mechanisms of extracellular miR-21 in glioma. TGF-β/Smad3 signaling was identified to participate in mediating the release of miR-21 from glioma cells. Further targeting TGF-β/Smad3 signaling using galunisertib, an inhibitor of the TGF-β type I receptor kinase, can attenuate the secretion of miR-21 from glioma cells. Taken together, CSF-based miR-21 might serve as a potential biomarker for diagnosing brain cancer, especially for patients with glioma. Moreover, extracellular levels of miR-21 were affected by exogenous TGF-β activity and galunisertib treatment.

Kai Qu,1,* Qing Pang,1,* Ting Lin,1 Li Zhang,2 Mingliang Gu,3 Wenquan Niu,4 Chang Liu,1,* Ming Zhang5 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China; 3Chinese Academy of Sciences Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Recent studies have showed interleukin 10 (IL-10) is a critical cytokine that determines antiviral immune response and is related to virus-associated cancers. However, whether genetically elevated circulating IL-10 levels are associated with the risk of human papilloma virus and Epstein–Barr virus-associated cancers (HEACs) is still unclear. Mendelian randomization method was implemented to meta-analyze available observational studies by employing IL-10 three variants (-592C>A, -819C>T, and -1082A>G) as instruments. Atotal of 24 articles encompassing 11,170 subjects were ultimately eligible for the meta-analysis. Overall, there was a significant association between IL-10 promoter variant -1082A>G and HEACs under allelic and dominant models (both PG was significant for nasopharyngeal cancer under allelic, homozygous genotypic and dominant models (all P

Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis.

Although overweight and obesity increase cancer risk, it is still controversial with respect to cancer mortality. In the current study, we enrolled 2670 patients of 14 tumor types from the Cancer Genome Atlas (TCGA) project, to identify the prognostic role of overweight and obesity in cancer patients. After dividing the patients into different groups by the body mass index (BMI), we found significant lower mortality in the obesity group. In addition, we also treat BMI value as a binary categorical variable or continuous variable, respectively. We found significant lower mortality in the higher BMI group. Furthermore, when focusing on each tumor type, cervical cancer and bladder cancer showed lower mortality in the patients with higher BMI values. Taken together, our results demonstrate that postdiagnosis obesity might indicate a better prognosis in cancer patients. However, these findings should be interpreted cautiously because of small sample size.

We previously found that chicken egg white extract could promote cell survival and proliferation. In the present study, we further separated this extract into its components to identify those primarily responsible for promoting cell proliferation. Components of differing molecular weight were separated from chicken egg white extract by ultrafiltration and 293T cell cultures were supplemented with various concentrations. The effects on cell proliferation were subsequently determined by a CellTiter 96 Aqueous One Solution Cell Proliferation Assay kit (Promega). We demonstrate that components from chicken egg white smaller than 3 kDa in size are able to function as active ingredients promoting cellular proliferation. This discovery may identify a new and convenient additive for cell culture media to promote cell growth and proliferation.

BACKGROUND: At present, the effect of western-medicine (WM) therapy to treat diabetic peripheral neuropathy (DPN) is limited. Moxibustion is a representative external treatment in traditional Chinese medicine that has been beneficial to DPN. We aim to systematically assess the efficacy and safety of moxibustion in treating DPN, following PRISMA guidelines. METHODS: Eight electronic databases were searched to acquire information on eligible trials published from inception to June 1, 2019. We included randomized controlled trials (RCTs) applying moxibustion therapy with a minimum of 14-days treatment duration for DPN patients compared with placebo, no intervention, or conventional WM interventions. The primary outcomes in our study include the sensory-nerve conduction velocity (SNCV) and motor-nerve conduction velocity (MNCV). We used the Cochrane Collaboration Risk of Bias tool to assess the methodological quality of eligible RCTs. Statistical analyses were conducted using Review Manager 5.3. Risk ratios (RR) and mean differences (MD) were calculated with a 95% confidence interval (CI). The χ test was applied to assess the heterogeneity. RESULTS: In total, 11 RCTs were included that involved 927 DPN patients. Compared with the control group, there was an increase in median MNCV (MD = 6.26, 95% CI 2.64-9.89, Z = 3.39, P = .0007) and peroneal MNCV (MD = 6.45, 95% CI 5.30-7.61, P 

Aim. Child-Pugh (CP) grade has been used to assess liver function and postoperative outcomes in biliary tract neoplasms. The aim of this study was to preliminarily explore the prognostic significance of an alternative model of liver function, called albumin-bilirubin (ALBI) grade, in patients with extrahepatic cholangiocarcinoma (EHC). Methods. A total of 109 advanced EHC patients, who received percutaneous transhepatic biliary stenting combined with iodine-125 seed implantation from January 2012 to April 2017 in our department, were enrolled. Preoperative clinical data were collected to calculate the CP and ALBI grades. The performance of ALBI score in predicting postoperative death was compared with that of CP score by using the receiver operating characteristic (ROC) curve. Kaplan-Meier analysis and Cox regression model were performed for overall survival (OS) analysis. Results. The median survival time of our cohort was 12 months, and the 1-year and 2-year survival rates were 56.9% and 12.8%, respectively. The area under the ROC curve of ALBI score for predicting death was significantly greater than the CP score (0.751, 95% CI: 0.641–0.861, P<0.001 vs. 0.688, 95% CI: 0.567–0.809, P<0.001). The univariate analysis revealed that the factors related to overall survival of EHC were carbohydrate antigen 19-9, total bilirubin, albumin, ALBI grade, and CP score. In multivariate analysis, ALBI grade (HR = 1.65, 95% CI: 1.04–2.61, P=0.032), but not CP score, was identified as an independent prognostic model. Conclusion. We demonstrated that the ALBI grade could be used as a predictor of survival in unresectable EHC patients.

We mainly aimed to preliminarily explore the prognostic values of nutrition-based prognostic scores in patients with advanced hilar cholangiocarcinoma (HCCA). We retrospectively analyzed 73 cases of HCCA, who underwent percutaneous transhepatic biliary stenting (PTBS) combined with 125I seed intracavitary irradiation from November 2012 to April 2017 in our department. The postoperative changes of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and albumin (ALB) were observed. The preoperative clinical data were collected to calculate the nutrition-based scores, including controlling nutritional status (CONUT), C-reactive protein/albumin ratio (CAR), and prognostic nutritional index (PNI). Kaplan–Meier curve and Cox regression model were used for overall survival (OS) analyses. The serum levels of TBIL, DBIL, ALT, AST, and ALP significantly reduced, and ALB significantly increased at 1 month and 3 months postoperatively. The median survival time of the cohort was 12 months and the 1-year survival rate was 53.1%. Univariate analysis revealed that the statistically significant factors related to OS were CA19-9, TBIL, ALB, CONUT, and PNI. Multivariate analysis further identified CA19-9, CONUT, and PNI as independent prognostic factors. Nutrition-based prognostic scores, CONUT and PNI in particular, can be used as predictors of survival in unresectable HCCA.

As a well-known traditional Chinese medicine (TCM) prescription, Xin-Sheng-Hua Granule (XSHG) has been applied in China for more than 30 years to treat postpartum diseases, especially anemia. However, underlying therapeutic mechanisms of XSHG for anemia were still unclear. In this study, plasma metabolomics profiling with UHPLC-QTOF/MS and multivariate data method was firstly analyzed to discover the potential regulation mechanisms of XSHG on anemia rats induced by bleeding from the orbit. Afterward, the compound-target-pathway network of XSHG was constructed by the use of network pharmacology, thus anemia-relevant signaling pathways were dissected. Finally, the crucial targets in the shared pathways of metabolomics and network pharmacology were experimentally validated by ELISA and Western Blot analysis. The results showed that XSHG could exert excellent effects on anemia probably through regulating coenzyme A biosynthesis, sphingolipids metabolism and HIF-1α pathways, which was reflected by the increased levels of EPOR, F2, COASY, as well as the reduced protein expression of HIF-1α, SPHK1, and S1PR1. Our work successfully explained the polypharmcological mechanisms underlying the efficiency of XSHG on treating anemia, and meanwhile, it probed into the potential treatment strategies for anemia from TCM prescription.

The article by Kirschbaum et al. (1) shows that temporary von Willebrand factor-mediated platelet influx in the liver remnant drives platelet-mediated liver regeneration (LR) following partial hepatectomy. Indeed, there is mounting evidence that platelet and endogenous factors are beneficial to hepatocyte regeneration in patients with hepatocellular carcinoma (HCC). Furthermore, platelet-increasing therapy has been recommended to improve LR following partial hepatectomy. However, we want to point out that, platelets may play adverse roles in the remnant liver of HCC and metastatic hepatic carcinoma (MHC) patients. This article is protected by copyright. All rights reserved.

Discovering a new cell transplantation approach for treating chronic renal insufficiency is a goal of many nephrologists. In vitro-cultured peripheral blood mononuclear cells (PBMCs) were reprogrammed into induced mesenchymal stem cells (iMSCs) by using natural inducing agents made in our laboratory. The stem cell phenotype of the iMSCs was then identified. Unilateral ureteral obstruction (UUO) was used to create an animal model of chronic renal insufficiency characterized by renal interstitial fibrosis. The induced and non-induced PBMCs were transplanted, and the efficacy of iMSCs in treating chronic renal insufficiency was evaluated using a variety of methods. The ultimate goal was to explore the effects of iMSC transplantation on the treatment of chronic renal insufficiency, with the aim of providing a new therapeutic modality for this disease.

Child-Pugh (CP) grade A patients with early stage hepatocellular carcinoma (HCC) are candidates for curative surgery, while some patients still have a poor outcome. The aim of this study was to investigate the prognostic values of 2 new evaluation models for liver function, named albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades, in CP grade A patients with HCC.In this retrospective cohort study, we reviewed 134 cases of CP grade A patients with hepatitis B-associated HCC who underwent radical surgery. ALBI and PALBI grades were calculated based on preoperative serologic examinations. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier curve and Cox regression. The prognostic performances of the models were estimated by using the concordance index (C-index).During a median follow-up time of 27 months, 27.6% (37/134) of patients died and 26.1% (35/134) experienced recurrence. Kaplan-Meier analyses showed that ALBI and PALBI grades were significantly associated with OS and RFS. Multivariate analyses further revealed that both ALBI and PALBI grades were independent predictors for survival. Furthermore, the prognostic values of the combination of tumor size with ALBI (C-index = 0.754, 95% confidence interval [CI]: 0.675-0.849) or with PALBI (C-index = 0.762, 95% CI: 0.664-0.844) may be comparable with both Barcelona Clinic Liver Cancer and Cancer of Liver Italian Program staging systems.The ALBI and PALBI grades, in particular the combination with tumor size, are effective models for discriminating survival in CP grade A patients with HCC.

Yan Deng, Qing Pang, Run-Chen Miao, Wei Chen, Yan-Yan Zhou, Jian-Bin Bi, Su-Shun Liu, Jing-Yao Zhang, Kai Qu, Chang Liu Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China Background: Pretreatment nutritional and immunological statuses play an indispensable role in predicting the outcome of patients with various types of malignancies. The purpose of this study is to evaluate the predictive value of albumin/globulin ratio (AGR) in overall survival (OS) and recurrence in patients with hepatocellular carcinoma (HCC) following radical hepatic carcinectomy. Patients and methods: This retrospective study included a total of 172 patients with HCC with complete medical and follow-up information between 2002 and 2012. AGR was calculated according to the following formula: AGR = albumin/globulin. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value. The associations of AGR with clinicopathological characteristics and prognosis were assessed. Further multivariate analysis using Cox regression model and subgroup analysis was performed to evaluate the predictive value. Results: Receiver operating characteristic curve determined 37.65, 31.99, and 1.48 as the optimal cutoff values of albumin, globulin, and AGR in terms of 5-year OS or death, respectively. On the basis of the cutoff value of AGR, all the patients were divided, respectively, into low-AGR (n=105) and high-AGR (n=67) groups. AGR was found to be significantly correlated with age, cancer embolus, international normalized ratio, and postoperative outcome (P

Background The establishment of a tree shrew model for systemic lupus erythematosus (SLE) provides a new method to evaluate the pathogenesis of autoimmune diseases. Methods Eighty tree shrews were randomly divided into four groups receiving either an intraperitoneal injection of pristane, lipopolysaccharide (LPS), or pristane and LPS, or no injection. Three weeks after injection, the SLE model tree shrews were divided into the model group and the treatment group. Tree shrews in the treatment group and the normal control group were infused with umbilical cord mesenchymal stem cells (UC-MSCs). The cells were labeled with DiR. Two weeks after transplantation, three groups of tree shrews were analyzed for urine protein, serum antinuclear antibodies and antiphospholipid, and inflammatory cytokine antibody microarray detection. The heart, liver, spleen, lung, and kidney were collected from the three groups and subjected to hematoxylin and eosin (HE) staining and detection of renal immune complex deposition. Results HE staining indicated pathology in the model group. Red fluorescence revealed immune complex deposition in the kidneys from the model group. Conclusions The combined intraperitoneal injection of pristane and LPS is the best way to induce SLE pathological changes. The pathological changes improved after UC-MSC treatment.

Qing Pang, Jian-Bin Bi, Zhi-Xin Wang, Xin-Sen Xu, Kai Qu, Run-Chen Miao, Wei Chen, Yan-Yan Zhou, Chang Liu Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Shaanxi Province, People’s Republic of China Background: Several hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC). We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT) and platelets in hepatitis B-associated HCC. Methods: We retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR) and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups. Results: During a median follow-up time of 45.0 months, a total of 88 (48.4%) patients died and 79 (43.4%) patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P

The aim of this study was to establish a tree shrew metabolic syndrome model and demonstrate the utility of MSCs in treating metabolic syndrome. We used tree shrew umbilical cord mesenchymal stem cell (TS-UC-MSC) transplantation for the treatment of metabolic syndrome to demonstrate the clinical application of these stem cells and to provide a theoretical basis and reference methods for this treatment. Tree shrew metabolic syndrome model showed significant insulin resistance, high blood sugar, lipid metabolism disorders, and hypertension, consistent with the diagnostic criteria. TS-UC-MSC transplantation at 16 weeks significantly reduced blood sugar and lipid levels, improved insulin resistance and the regulation of insulin secretion, and reduced the expression levels of the pro-inflammatory cytokines IL-1 and IL-6 (P

Aim Multiple Organ Dysfunction Syndrome (MODS) is characterized as progressive and uncontrolled inflammatory response which involves activation of inflammatory cascades, cytokines release, and endothelial dysfunction, leading to deterioration of several organ functions. Curcumin is a natural polyphenol related to the yellow color of turmeric and has been reported to exert an anti-inflammatory, anti-oxidative, and anti-tumor effect. We conducted the study to investigate the effects of curcumin in non-septic MODS caused by zymosan in mice model. Method The mice were randomly allocated into five groups (six mice per group): control group (treated with physiological saline, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), Curcumin group (200 mg/kg, suspended in DMSO, in a final volume of 0.1 mL, used for 3 days daily before and 1 h after physiological saline treatment), Zymosan+DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after zymosan treatment) and Zymosan+ Curcumin group (treated with curcumin, suspended in DMSO at a dose of 0.1 mL daily for 3 days before and 1 h after zymosan treatment).Mice in groups were sacrificed, and then the blood and tissues were collected to evaluate the severity of acute peritonitis, tissue histopathological changes, NO formation, oxidative stress, PMN infiltration, cytokines production, organ function, and NF-κB activation 18 h after when zymosan or physiological saline was injected. In another set of experiments, the mice were also grouped (20 mice per group) for monitoring the loss of body weight and mortality for 7 days after zymosan or physiological saline administration. Results Curcumin induces a significant reduction of the volume exudate and the neutrophil infiltration. It also could exhibit an outstanding protective effect against histopathological injury by decreasing the NO formation, oxidative stress, cytokines production, and infiltration of inflammatory cells. The organ function is also improved by administration of curcumin. Moreover, the activation of NF-κB is attenuated by curcumin in the MODS mice model, suggesting that curcumin attenuated the zymosan-induced MODS via inhibiting the expression of NF-κB possibly. In addition, curcumin-treated mice were shown to alleviate the severity of MODS characterized by a minor systemic toxicity, less body weight loss, and lower mortality caused by zymosan administration. Conclusion Curcumin attenuates zymosan-induced MODS.

Different organ preservation methods are key factors influencing the results of liver transplantation. In this study, the outcomes of experimental models receiving donation after cardiac death (DCD) livers preserved through machine perfusion (MP) or static cold storage (CS) were compared by conducting a meta-analysis. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to compare pooled data from two animal species. Twenty-four studies involving MP preservation were included in the meta-analysis. Compared with CS preservation, MP can reduce the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and hyaluronic acid (HA) and the changes in liver weight. By contrast, MP can enhance bile production and portal vein flow (PVF). Alkaline phosphatase (ALP) levels and histological changes significantly differed between the two preservation methods. In conclusion, MP of DCD livers is superior to CS in experimental animals.

We performed weighted gene coexpression network analysis (WGCNA) to gain insights into the molecular aspects of hepatocellular carcinoma (HCC). Raw microarray datasets (including 488 samples) were downloaded from the Gene Expression Omnibus (GEO) website. Data were normalized using the RMA algorithm. We utilized the WGCNA to identify the coexpressed genes (modules) after non-specific filtering. Correlation and survival analyses were conducted using the modules, and gene ontology (GO) enrichment was applied to explore the possible mechanisms. Eight distinct modules were identified by the WGCNA. Pink and red modules were associated with liver function, whereas turquoise and black modules were inversely correlated with tumor staging. Poor outcomes were found in the low expression group in the turquoise module and in the high expression group in the red module. In addition, GO enrichment analysis suggested that inflammation, immune, virus-related, and interferon-mediated pathways were enriched in the turquoise module. Several potential biomarkers, such as cyclin-dependent kinase 1 (CDK1), topoisomerase 2α (TOP2A), and serpin peptidase inhibitor clade C (antithrombin) member 1 (SERPINC1), were also identified. In conclusion, gene signatures identified from the genome-based assays could contribute to HCC stratification. WGCNA was able to identify significant groups of genes associated with cancer prognosis.

We aimed to assess the therapeutic effect of reimplantation of biliary metal stents by percutaneous transhepatic cholangial drainage (PTCD) in patients with recurrent malignant obstructive jaundice (MOJ). Furthermore, we explored the prognostic value of inflammation-based markers in these patients.We reviewed 33 cases of recurrent MOJ after implantation of biliary metal stents by PTCD, all of which underwent reimplantation of stents under digital subtraction angiography guidance. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin were compared between before and after reimplantation (1 week, 1 month, and 3 months postoperatively). Preoperative clinical data were collected to calculate the inflammation-based markers, including systemic immune-inflammation index (SII, neutrophil × platelets/ lymphocyte), platelets-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). The primary outcome was overall survival (OS), which was estimated by the Kaplan-Meier method and Cox regression analysis.The levels of ALT, AST, total bilirubin, and direct bilirubin significantly reduced after the reimplantation operation. During a median follow-up time of 10 months, 18 (54.5%) patients died. Gender, albumin, SII, PLR, NLR, and MLR were found to be associated with OS by the log-rank test and univariate analysis. Multivariate Cox analysis identified elevated levels of SII and PLR as significant factors for predicting poor OS.Reimplantation is clinically feasible in patients with recurrent MOJ after implantation of biliary metal stents. SII and PLR are independent, useful inflammation-based prognostic models for predicting outcomes in these patients.