Unveiling the therapeutic potential of epigallocatechin gallate in liver cancer: insights from network pharmacology and in vitro assays.

Epigallocatechin gallate (EGCG) is a prominent catechin found in green tea polyphenols and has shown promising anti-tumor properties. However, the exact regulatory mechanism of EGCG on liver cancer is not fully revealed. In this study, we conducted integrative analyses using the SwissTargetPrediction and GeneCards repositories, which identified 98 targets. These targets were used to construct a protein-protein interaction network using STRING and visualised with Cytoscape. Central to this network are hub proteins, notably TNF and PIK3CA, suggesting pivotal roles in the therapeutic landscape. Gene Ontology (GO) enrichment analysis unveiled 1,570 biological terms with a notable preponderance within oxidative stress response processes. Complementary pathway enrichment via the Kyoto Encyclopaedia of Genes and Genomes (KEGG) highlighted 134 pathways, with the PI3K-Akt pathway emerging as prominent. In silico molecular docking supported these findings, revealing binding energies of EGCG-target complexes below -7.0 kcal/mol, indicative of robust interactions. Moreover, cellular assays including CCK-8, wound-healing, and Transwell modalities, established EGCG's inhibitory concentration-dependent effects on HepG2 cell proliferation, migration, and invasion. Apoptotic assays affirmed by FACS, evidenced enhanced apoptosis with escalating EGCG concentrations, underpinned by modulations in caspase activity and apoptotic protein levels. Notably, Western blot analysis demonstrated the attenuation of the PI3K/AKT signalling cascade by EGCG, paralleling the inhibitory profile of LY294002. These multifaceted inhibitory effects underscore EGCG's potential as an anti-tumor agent, deploying a strategic blockade of oncogenic pathways and augmenting apoptotic mechanisms, which provide a strong rationale for its application in liver cancer therapeutics.

Cholecystohepatic shunt pathway reduces secondary bile acid accumulation to enhance natural killer T cell-mediated anti-hepatocellular carcinoma immunity.

BACKGROUND AND AIM: The impact of cholecystectomy, which blocks the cholecystohepatic shunt pathway (CHSP), on the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Hepatic secondary bile acids (BAs) inhibit natural killer T (NKT) cell-mediated immunity against HCC, and the regulation of homeostasis of hepatic secondary BAs is controlled by the CHSP. However, the influence of CHSP on NKT cell-mediated immunity against HCC remains unclear. METHODS: The clinical data of hospitalized patients undergoing HCC resection were collected. Meanwhile, an in situ HCC mouse model was established, and the CHSP was augmented using oleanolic acid (OA). RESULTS: After 1:1 propensity score matching, Cox regression analysis revealed that cholecystectomy was an independent risk factor for HCC recurrence after hepatectomy (P = 0.027, hazard ratio: 1.599, 95% confidence interval: 1.055-2.422). Experimentally, when OA enhanced CHSP, a significant decrease was observed in the accumulation of secondary BAs in the livers of mice. Additionally, a significant increase was observed in the levels of C-X-C ligand 16 and interferon γ in the serum and tumor tissues. Further, the percentage of C-X-C receptor 6 (+) NKT cells in the tumor tissues increased significantly, and the growth of liver tumors was inhibited. CONCLUSIONS: This clinical study revealed that cholecystectomy promoted the recurrence after radical hepatectomy in patients with HCC. Preserving the normal-functioning gallbladder as much as possible during surgery may be beneficial to the patient's prognosis. Further investigation into the mechanism revealed that CHSP enhanced NKT cell-mediated immunity against HCC by reducing the hepatic accumulation of secondary BAs.

Enhancing Interfacial Strength and Wettability for Wide-Temperature Sodium Metal Batteries.

Development of high-performance sodium metal batteries (SMBs) with a wide operating temperature range (from -40 to 55 °C) is highly challenging. Herein, an artificial hybrid interlayer composed of sodium phosphide (Na3 P) and metal vanadium (V) is constructed for wide-temperature-range SMBs via vanadium phosphide pretreatment. As evidenced by simulation, the VP-Na interlayer can regulate redistribution of Na+ flux, which is beneficial for homogeneous Na deposition. Moreover, the experimental results confirm that the artificial hybrid interlayer possesses a high Young's modulus and a compact structure, which can effectively suppress Na dendrite growth and alleviate the parasitic reaction even at 55 °C. In addition, the VP-Na interlayer exhibits the capability to knock down the kinetic barriers for fast Na+ transportation, realizing a 30-fold decrease in impedance at -40 °C. Symmetrical VP-Na cells present a prolonged lifespan reaching 1200, 500, and 500 h at room temperature, 55 °C and -40 °C, respectively. In Na3 V2 (PO4 )3 ||VP-Na full cells, a high reversible capacity of 88, 89.8, and 50.3 mAh g-1 can be sustained after 1600, 1000, and 600 cycles at room temperature, 55 °C and -40 °C, respectively. The pretreatment formed artificial hybrid interlayer proves to be an effective strategy to achieve wide-temperature-range SMBs.

Protective effect of pinocembrin from Penthorum chinense Pursh on hepatic ischemia reperfusion injury via regulating HMGB1/TLR4 signal pathway.

Hepatic ischemia-reperfusion injury (HIRI) is of common occurrence during liver surgery and transplantation. Pinocembrin (PIN) is a kind of flavonoid monomer extracted from the local traditional Chinese medicine Penthorum chinense Pursh (P. chinense). However, the effect of PIN on HIRI has not determined. We investigated the protective effect and potential mechanism of PIN against HIRI. Model mice were subjected to partial liver ischemia for 60 min, experimental mice were pretreated with PIN orally for 7 days, and H2 O2 -induced oxidative damage model in AML12 hepatic cells was established in vitro. Histopathologic analysis and serum biochemical levels revealed that PIN had hepatoprotective activities against HIRI. The variation of GSH, SOD, MDA, and ROS levels indicated that PIN treatments attenuated oxidative stress in tissue. PIN pretreatment obviously ameliorated apoptosis, and restrained the expression of HMGB1 and TLR4 in vivo. In vitro, compared with H2 O2 group, the contents of ROS, mitochondrial membrane potential, apoptotic cells, and Bcl-2 protein were decreased, while the Bax protein expression was increased. Moreover, HMGB-1 small interfering RNA test and western blotting showed that PIN pretreatment reduced HMGB1 and TLR4 protein levels. In conclusion, PIN pretreatment effectively protected hepatocytes from HIRI and inhibited the HMGB1/TLR4 signaling pathway.

A Multifunctional Interphase Layer Enabling Superior Sodium-Metal Batteries under Ambient Temperature and -40 °C.

The sodium (Na)-metal anode with high theoretical capacity and low cost is promising for construction of high-energy-density metal batteries. However, the unsatisfactory interface between Na and the liquid electrolyte induces tardy ion transfer kinetics and dendritic Na growth, especially at ultralow temperature (-40 °C). Herein, an artificial heterogeneous interphase consisting of disodium selenide (Na2 Se) and metal vanadium (V) is produced on the surface of Na (Na@Na2 Se/V) via an in situ spontaneous chemical reaction. Such interphase layer possesses high sodiophilicity, excellent ionic conductivity, and high Young's modulus, which can promote Na-ion adsorption and transport, realizing homogenous Na deposition without dendrites. The symmetric Na@Na2 Se/V cell exhibits outstanding cycling life span of over 1790 h (0.5 mA cm-2 /1 mAh cm-2 ) in carbonate-based electrolyte. More remarkably, ab initio molecular dynamics simulations reveal that the artificial Na2 Se/V hybrid interphase can accelerate the desolvation of solvated Na+ at -40 °C. The Na@Na2 Se/V electrode thus exhibits exceptional electrochemical performance in symmetric cell (over 1500 h at 0.5 mA cm-2 /0.5 mAh cm-2 ) and full cell (over 700 cycles at 0.5 C) at -40 °C. This work provides an avenue to design artificial heterogeneous interphase layers for superior high-energy-density metal batteries at ambient and ultralow temperatures.

Effect of FXR agonist GW4064 in the treatment of hilar cholangiocarcinoma in rats.

The study objective was to observe the treatment effect of the farnesoid X receptor (FXR) agonist GW4064 in a rat model of hilar cholangiocarcinoma to explore a new therapeutic target for gene therapy for hilar cholangiocarcinoma. Eighty male Wistar rats were randomly divided into four groups (treatment group, model group, control group and sham operation group, 20 rats in each group). The four groups were fed a standard diet. The treatment group and the model group were injected with a suspension of cholangiocarcinoma QBC939 cells into the hilar bile duct with a microsyringe, the control group was injected with normal saline, and the sham operation group was not injected with anything. A modified tail suspension test (TST) was used to evaluate the vitality of the rats. At 4 weeks, one rat in the treatment group and model group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma occurred in the treatment group and model group. Then, the treatment group was injected with GW4064 intraperitoneally at a dose of 50 mg/kg/day. One week after injection, the rats in the four groups were euthanized. Pathological examination confirmed that tumours had formed, and hilar bile duct tissues were taken from the four groups. FXR, Bsep, Ntcp and NF-κB expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. After three weeks, the rats in the treatment group and model group ate less, and their weight was significantly reduced. Six weeks later, hilar cholangiocarcinoma was detected in the treatment group and model group. After treatment with GW4064, the ratios of FXR/GAPDH mRNA, Bsep/GAPDH mRNA, Ntcp/GAPDH mRNA and NF-κBp65/GAPDH mRNA were significantly different among the four groups. Under a light microscope, FXR protein reacted with anti-FXR antibody, Bsep protein reacted with anti-Bsep antibody, Ntcp protein reacted with anti-Ntcp antibody and NF-κBp65 protein reacted with anti-NF-κBp65 antibody, and they showed granular expression. Every pathological section included 4,800 cells, and there were different numbers of positive cells in each group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues. GW4064 increased the expression of FXR in tumour tissues. These findings suggest that FXR may be a new therapeutic target and that GW4064 may be helpful in the treatment of hilar cholangiocarcinoma.

N-Acetyl-l-tryptophan inhibits CCl4-induced hepatic fibrogenesis via regulating TGF-ß1/SMAD and Hippo/YAP1 signal.

BACKGROUND: Although liver fibrosis is a key pathologic process in many liver diseases, therapeutic approaches for inhibiting liver fibrosis are still very limited. N-Acetyl-l-tryptophan (l-NAT) has a hepatoprotective effect via inhibiting the destruction of liver cells, enhancing cell viability and reducing the inflammation. However, the effect of l-NAT on liver fibrosis is not determined. PURPOSE: The present study investigated the effect of l-NAT on liver fibrosis and explored it potential molecular mechanism. METHODS: To address this concern, this study was carried out via fibrotic mice model induced by CCl4 and many approaches such as various histological staining methods, western blot assay, etc. RESULT: l-NAT decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in fibrotic mice model induced by carbon tetrachloride (CCl4). Histological staining showed that l-NAT ameliorated liver injury and fibrosis, and reduced the expression of α-smooth muscle actin (α-SMA) and Collagen I protein. l-NAT also attenuated apoptosis by down-regulating the level of pro-apoptotic protein Bax and up-regulating that of anti-apoptotic protein Bcl-2. Moreover, l-NAT inhibited the expressions of TGF-ß1/SMAD and matrix metalloproteinase 9 (MMP9) proteins, and reversed the expression of YAP1 protein in CCl4-induced liver fibrosis. CONCLUSION: These results clearly demonstrated that l-NAT attenuated CCl4-induced liver fibrosis in mice, and this protective mechanism might relate to TGF-ß1/SMAD and Hippo/YAP1 signaling pathway. Thus, this study provided data basis for the prevention and treatment of liver fibrosis.

A sodiophilic VN interlayer stabilizing a Na metal anode.

Sodium (Na) metal is a very encouraging anode material for next-generation rechargeable batteries owing to its high specific capacity, earth-abundance and low-cost. However, the application of Na metal anodes (SMAs) is hampered by dendrite growth and "dead" Na formation caused by the uncontrollable Na deposition, leading to poor cycle life and even safety concerns. Herein, a high-performance Na anode is designed by introducing an artificial VN interlayer on the Na metal surface (Na/VN) by a simple mechanical rolling process to regulate Na nucleation/deposition behaviors. The density functional theory (DFT) and experiment results uncover that the VN possesses high "sodiophilicity", which can facilitate the initially homogeneous Na nucleation and cause Na to distribute evenly on the VN interlayer. Therefore, uniform Na deposition with dendrite-free morphology and prolonged cycling lifespan (over 1060 h at 0.5 mA cm-2/1 mA h cm-2) can be realized. Moreover, the full cell assembled by coupling a Na3V2(PO4)3 (NVP) cathode and Na/VN anode presents superior cycling performance (e.g., 96% capacity retention even after 800 cycles at 5C). This work provides a promising direction for regulating Na nucleation and deposition to achieve dendrite-free metal anodes.

NTCP Change in Rats of Hilar Cholangiocarcinoma and Therapeutic Significance.

Background: The study aims to detect the expression of Na+/taurocholate cotransporter polypeptide in hilar cholangiocarcinoma of rat model, to provide a new therapeutic target for gene therapy of hilar cholangiocarcinoma. Methods: 60 male Wistar rats (weighing 190 ± 8 g) were randomly divided into 3 groups (experimental group, control group, and sham operation group; 20 rats in each group). The 3 groups were fed with standard diet. The QBC939 cell suspension of cholangiocarcinoma was injected into the hilar bile duct in the experimental group with a micro syringe. The control group was injected with normal saline, and the sham operation group was not injected with any drugs. Comprehensive behavior score and Basso Beattie Bresnahan were used to evaluate the mental state and exercise of rats every day. At 5 weeks, one rat in the experimental group was killed, and the changes in hilar bile duct were recorded. The procedure was repeated at one and half months. After one and half months, hilar cholangiocarcinoma only occurred in the experimental group. Pathological examination confirmed the formation of tumor, and hilar bile duct tissues were taken from the 3 groups. Na+/taurocholate cotransporter polypeptide expression in hilar bile duct was detected by real-time polymerase chain reaction and immunohistochemistry. Results: After 2 weeks, the rats in experimental group ate less, and their weight was significantly reduced compared with the other 2 groups. One and half months later, hilar cholangiocarcinoma was detected in 16 rats in the experimental group. The levels of alanine aminotransferase and aspartate transaminase in the experimental group were higher than those in the other 2 groups. The ratio of Na+/taurocholate cotransporter polypeptide/GAPDH mRNA in hilar cholangiocarcinoma, control group, and sham operation group was significantly different. Under the light microscope, Na+/taurocholate cotransporter polypeptide protein reacted with anti-Na+/taurocholate cotransporter polypeptide antibody and showed granular expression. Every pathological section included 4800 cells. 3823 positive cells were in the experimental group, 1765 positive cells were in the control group, and 1823 positive cells were in the sham operation group. Conclusions: Na+/taurocholate cotransporter polypeptide expression in hilar cholangiocarcinoma of rats was significantly higher than normal hilar bile duct tissues, suggesting that drugs targeting Na+/taurocholate cotransporter polypeptide may be a new strategy for the treatment of hilar cholangiocarcinoma.

Significant Succession of Intestinal Bacterial Community and Function During the Initial 72 Hours of Acute Pancreatitis in Rats.

Acute pancreatitis (AP) is followed by structural and functional changes in the intestine, resulting from microbiome dysbiosis. However, it remains unclear how gut microbiome changes within the initial 72h of onset. In this study, severe acute pancreatitis (SAP), mild acute pancreatitis (MAP), and sham operation (SO) were replicated in rat models. 16S ribosomal RNA gene sequencing was used to explore the gut bacteria community. The predicted Cluster of Orthologous Genes (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways were associated with the 16S rRNA profiles. Compared to the SO group, significant community succession was found during the initial 72h in AP group. At 72 h after AP induction, the Firmicutes/Bacteroidetes (F/B) ratios were significantly different, with the highest ratio in SAP group and the lowest in MAP group. Lactobacillus was the most abundant genus, but it nearly disappeared in SAP rats at 72 h. Clostridiaceae 1 and Clostridium sensu stricto 1 were significantly enriched in AP group. Bacteroidales S24-7 and Bacteroidales S24-7 group norank were enriched in MAP group, while Collinsella, Morganella, and Blautia were enriched in SAP group. Lactobacillus was significantly correlated with nine COGs. Nine COGs showed significant differences between AP group and SO group. Moreover, four COGs showed significant differences between the MAP and SAP groups. KEGG Level_3 pathways propanoate metabolism (Ko00640) in AP group was significantly higher than that in SO group. The aspartate‒ammonia ligase and four KEGG orthology terms of the AP group were lower than that in the SO group, respectively. All these results suggest that the intestinal bacterial community structure and function was changed during the initial 72h in AP rats. The intestinal F/B ratio and the relative abundance of Lactobacillus could be potential markers for early diagnosis of MAP and SAP. The genus Clostridium sensu stricto 1 was the most enriched genus in AP, and may be an important marker for AP.

Extracellular Vesicles from miR-148a-5p-Enriched Bone Marrow Mesenchymal Stem Cells Relieve Hepatic Fibrosis by Targeting Smad4.

Liver fibrosis is a hallmark feature of many chronic liver diseases, which is the leading cause of morbidity and mortality worldwide. Bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles have been applied in many diseases. In this study, we aimed to explore the specific mechanism of extracellular vesicles from BMSCs in liver fibrosis. Bioinformatics analysis was employed to screen miRNA and its target mRNA. Sirius Red staining was carried out to examine fibrosis in liver tissues. Extracellular vesicle morphology was assessed using Transmission Electron Microscopy. Quantitative real-time PCR (qRT-PCR) and western blotting analysis were performed to detect the expressions of miR-148a-5p, Smad4, transforming growth factor-ß1 (TGF-ß1), tissue inhibitor of metalloproteinase 1 (TIMP-1), Collagen I, α-smooth muscle actin (α-SMA), and extracellular vesicle markers CD9, TSG101, CD63, and calnexin. Dual-luciferase report gene assay was used for the luciferase activity analysis. Bioinformatics analysis revealed miR-148a-5p as a regulator in liver fibrosis. QRT-PCR results indicated that miR-148a-5p was lowly expressed in both thioacetamide (TAA)-induced mice and TGF-ß1-activated hepatic stellate cells. Extracellular vesicles from miR-148a-5p enriched BMSCs downregulated the mRNA and protein levels of TGF-ß1, TIMP-1, Collagen I, and α-SMA. Further bioinformatics analysis indicated that Smad4 was related to liver fibrosis. Furthermore, the dual-luciferase report gene assay confirmed the binding relationship between miR-148a-5p and Smad4. Extracellular vesicles from miR-148a-5p enriched BMSCs attenuated hepatic fibrosis in liver fibrosis by targeting Smad4.

Comparison of Primary Suture and T-Tube Drainage After Laparoscopic Common Bile Duct Exploration Combined with Intraoperative Choledochoscopy in the Treatment of Secondary Common Bile Duct Stones: A Single-Center Retrospective Analysis.

Objective: To compare the safety and feasibility of T-tube drainage and primary suture after laparoscopy combined with choledochoscopy in the treatment of secondary choledocholithiasis. Methods: The clinical data of patients who underwent laparoscopic choledochoscopy combined with choledochoscopic common bile duct exploration (LCBDE) for secondary choledocholithiasis from June 2015 to June 2020 were analyzed retrospectively. According to the different treatment method of common bile duct (CBD) incision, the patients were divided into a T-tube drainage group and a primary suture group. The preoperative clinical characteristics, results of preoperative liver function tests (LFTs), LFTs on the first day after the operation and the fourth day after the operation, operation time, intraoperative bleeding, postoperative complications, and times of postoperative hospital stay were compared between the two groups. Results: There was no significant difference in preoperative clinical data, preoperative LFTs, and postoperative complications between the two groups (P > .05). However, primary suture demonstrated significant advantages (P < .05) in terms of the operation time, intraoperative blood loss, postoperative hospital stay, and other related factors. Bilirubin levels on the first day after the operation and the fourth day after the operation between the two groups suggested that T-tube drainage reduces bilirubin in the short term, but that long-term bilirubin draining is similar between the two strategies. Univariate and multivariate analyses showed that choledochal diameter less than 8 mm was an independent risk factor for bile leakage. Conclusions: Laparoscopy combined with intraoperative choledochoscopic CBD exploration is superior to T-tube drainage in terms of the operation time, intraoperative blood loss, and postoperative hospital stay. The ability of reducing bilirubin by traditional T-tube drainage is indeed better than that of primary suture in the early stage after operation, but there is no difference in long-term outcome between the two groups. Choledochal diameter ≤8 mm was an independent risk factor for bile leakage. To summarize, LCBDEs primary suture for secondary choledocholithiasis is safe and feasible.

Enhanced Store-Operated Ca2+ Signal of Small Intestinal Smooth Muscle Cells Accelerates Small Bowel Transit Speed in Type 1 Diabetic Mouse.

Aims: The underlying mechanism of diabetic enteropathy, a common complication of type 1 diabetes, remains unclear. Store-operated Ca2+ entry (SOCE) is a ubiquitous type of Ca2+ influx involved in various cellular functions. Here, we show that SOCE-related stromal interaction molecule 1 (STIM1) and Orai1 participate in inappropriate cellular Ca2+ homeostasis, augmenting agonist-induced small intestinal smooth muscle contraction and small bowel transit speed in a mouse model of type 1 diabetes. Methods and Results: We used small interfering (si)RNA to suppress STIM1 and Orai1 proteins, and employed intracellular Ca2+, small intestinal contraction and intestinal transit speed measurement to investigate the functional change. We found that SOCE activity and Orai1 and STIM1 expression levels of small intestinal smooth muscle were significantly increased in cells cultured in high glucose medium or in diabetic mice. Gastrointestinal transit speed and SOCE-mediated contractions were markedly increased in diabetic mice; Knocking down Orai1 or STIM1 with siRNA rescued both alterations in diabetic mice. However, the Orai1-large conductance Ca2+-activated K+ (BKCa) channel interaction was decreased in diabetic mice, and suppressing Orai1 expression or inhibiting the BKCa channel increased agonist-induced small intestinal contractions in normal mice. Conclusion: We concluded that the increased SOCE caused by excessive STIM1 and Orai1 expression and decreased Orai1-BKCa interaction augmented small intestinal smooth muscle contraction and accelerated small bowel transit speed in diabetic mice. This finding demonstrates a pathological role for SOCE in diabetic enteropathy and provides a potential therapeutic target for diabetic enteropathy.

The Dietary Supplement γ-Oryzanol Attenuates Hepatic Ischemia Reperfusion Injury via Inhibiting Endoplasmic Reticulum Stress and HMGB1/NLRP3 Inflammasome.

The purpose of this study is to investigate the protective effect of γ-oryzanol (ORY) against hepatic ischemia reperfusion (HIR) injury and the potential protective mechanisms of ORY. ORY is an important biologically active ingredient isolated from rice bran oil, which has anti-inflammatory and antiapoptotic effects. However, it is still unknown whether ORY can protect the liver from the HIR damage. In this study, ORY was administered orally for seven days, after which the animals were subjected to liver ischemia for 60 minutes and reperfused for 6 hours. Related indicators were analyzed. The results showed that ORY pretreatment significantly reduced the levels of AST and ALT, relieved hepatocellular damage and apoptosis, and attenuated the exhaustion of SOD and GSH and accumulation of MDA and MPO. Interestingly, ORY treatment could significantly decreased ER stress. Furthermore, ORY pretreatment remarkably reduced the protein expressions of HMGB1, NLRP3, caspase-1 (p20), and IL-1ß to protect the liver from I/R-induced inflammasome activation and apoptosis. In conclusion, we demonstrated the potential effect of ORY in modulating oxidative stress, endoplasmic reticulum stress, and inflammasome activation during HIR.

Luzhou-Feier powder reduces inflammatory response and improves intestinal immune barrier in rats with severe acute pancreatitis.

As we know, nutritional support plays a key role in the treatment of severe acute pancreatitis (SAP). Since total parenteral nutrition (TPN) was discovered, the mortality of SAP had been greatly reduced. But researchers recently demonstrated that the prognosis of SAP could be improved by early enteral nutrition (EEN), which has been a priority for nutritional support in patients with SAP. However, implementation of total enteral nutrition is often challenging in the early stage of SAP. If the enteral nutrition is overused, the burden on the gastrointestinal tract will be aggravated. Under such circumstances, the combination of enteral and parenteral nutrition for nutritional support of SAP patients would be a better choice. Therefore, in this study, we compared the efficacy of two enteral nutrition agents: traditional nutritional supplement named Luzhou-Feier powder (LZ-FP) and enteral nutritional suspension (TPF) combined with parenteral nutrition to total parenteral nutrition (TPN) in the treatment of SAP rats. Our analysis revealed that the combination of enteral nutrition and parenteral nutrition was more effective than TPN in SAP. And LZ-FP met the requirements for enteral nutrition of SAP supporting its clinical application in SAP. PRACTICAL APPLICATIONS: Luzhou-Feier powder (LZ-FP) is a traditional Chinese nutritional supplement that was originally developed as a nutritional supplement for infants and is currently used for nutritional support in patients with chronic and consumptive diseases. Our research investigated the effect and its possible mechanisms of LZ-FP as early trophic enteral nutrition in SAP rats and compared it with TPF and TPN which have been used clinically. We found that LZ-FP helped to reduce inflammatory response and improve the intestinal immune barrier of SAP. The curative effect of LZ-FP was comparable to that of TPF. And this effect may be achieved by inducing the secretion of gut hormones. Our research indicates that LZ-FP should be considered as an enteral nutrition preparation for SAP.

Bsep expression in hilar cholangiocarcinoma of rat model.

Develop a rat model of hilar cholangiocarcinoma for detecting bile salt export pump (Bsep) expression in hilar cholangiocarcinoma tissues, in order to provide a new therapeutic target for the gene therapy of hilar cholangiocarcinoma. Sixty male Wistar rats (body weight, 190 ± 8 g) were randomly divided into three groups (the experimental group, the control group and the sham operation group, n = 20 each) as follows: The three groups were fed a standard diet, the experimental group was injected by cholangiocarcinoma QBC939 cell suspension along the hilar bile duct into the bile duct bifurcation with microsyringe, the control group was injected by normal saline, the sham operation group did not inject anything. Every day assess the rats' mental state, diet, and motion by using Basso-Beattie-Bresnahan and combined behavioral score. At 4 weeks, one rat of the experimental group was sacrificed after it was administered anesthesia, and we recorded changes in hilar bile duct size, texture, and form. This procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma developed only in the experimental group, thereby establishing an experimental model for studying QBC939-induced hilar cholangiocarcinoma. Tumor formation was confirmed by pathological examination, and hilar bile duct tissues were harvested from both the groups. A real-time polymerase chain reaction assay and an immunohistochemical assay were used to analyze the expression of Bsep in hilar bile duct tissues of each group. From the second week, the rats in experimental group began to eat less, and their body mass decreased compared with control group and sham operation group. After 6 weeks, we detected hilar cholangiocarcinoma in the hilar bile duct tissues of 18 rats (90%) in the experimental group. In the experimental group with hilar cholangiocarcinoma, we found that the levels of total cholesterol, total bilirubin, and direct bilirubin were higher compared with those in the control group and sham operation group. Simultaneously, muddy stones emerged from the bile ducts of rats in the experimental group. The Bsep/Gapdh mRNA ratio in hilar cholangiocarcinoma, control group and sham operation group differed markedly. Light microscopy revealed a granular pattern of Bsep protein expression which reacted with the anti-Bsep antibody. Each section was randomly divided into six regions, with 80 cells were observed in every region. Sections with > 10% positive cells were designated positive, Sections with < 10% positive cells were designated negative. Each group included 4800 cells. In the experimental group, 1200 cells (25%) were positive, in the control group, 3648 cells (76%) were positive and in the sham operation group 3598 cells (75%) were positive, and this difference was statistically significant. Bsep expression significantly decreased in hilar cholangiocarcinoma of rats than those in control group and sham operation group, suggesting that drugs targeting Bsep are a new strategy for hilar cholangiocarcinoma.

Effects of remote ischemic preconditioning on liver injury following hepatectomy: a systematic review and meta-analysis of randomized control trials.

The protective effect of remote ischemic preconditioning (RIPC) against liver ischemia-reperfusion injury caused by hepatectomy remains controversial. We conducted this meta-analysis to evaluate the effectiveness and safety of RIPC strategies. PubMed, SinoMed, Embase, Cochrane Library, Medline, and Web of Science databases were searched for randomized controlled trials (RCT) that assessed the effectiveness and safety of RIPC strategies. The primary outcomes were operation time, index of liver function on postoperative day (POD) 1, postoperative complications, and postoperative hospital stay. The pooled odds ratios and weighted mean differences at 95% confidence interval (95% CI) were estimated using a fixed-effects or random-effects model. A total of 459 patients were included in seven RCTs. The alanine aminotransferase (ALT) and alanine aminotransferase (AST) values on POD1 were significantly different between the RIPC group and the N-RIPC group (P = 0.009 and P = 0.02, respectively). However, the heterogeneity was significant (I2 = 84% and I2 = 86%), and the results of a sensitivity analysis were unstable. There was no significant difference in the total bilirubin levels (P = 0.25) between the two groups on POD1. Subgroup analysis revealed no significant difference in the AST and ALT levels on POD1 between the RIIPC group and the N-RIPC group, regardless of whether the vascular control technique was used (all P > 0.05). Based on current evidence, RIPC does not alleviate liver injury caused by IRI after hepatectomy.

Meta-analysis of infrahepatic inferior vena cava clamping combined with the pringle maneuver during hepatectomy.

This meta-analysis was conducted to evaluate the effectiveness and safety of infrahepatic inferior vena cava clamping combined with the Pringle maneuver during. hepatectomies. Clinical studies were retrieved from the PubMed, Embase, Cochrane Library, Medline and Web of Science databases. Study-specific effect sizes and their 95% confidence intervals (CIs) were combined to calculate the pooled value using a fixed-effects or random-effects model.Nine studies with 1008 patients in total were included. The infrahepatic inferior vena cava clamping combined with Pringle maneuver group experienced less total operative blood loss (mean difference [MD] = -327.11; 95% CI: -386.50-267.72; P < 0.00001), less blood loss during transection (MD = -270.19; 95% CI: -344.99-195.38; P < 0.00001), fewer blood transfusions (odds ratio [OR] = 0.36; 95% CI: 0.25-0.53;P < 0.00001) and fewer postoperative complications (OR = 0.70; 95% CI: 0.52-0.95; P = 0.02) than did the control group. Operative time (MD = 8.54; 95% CI: 4.68-12.40; P < 0.0001) was similar in both groups. liver transection time,hospital stay, postoperative liver function and renal function did not differ between groups.Applying infrahepatic inferior vena cava clamping combined with the Pringle maneuver can effectively reduce intraoperative bleeding, blood transfusion rates, and postoperative complications, while adding minimal time to the operation.