Chen's penetrating-suture technique for pancreaticojejunostomy following pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most serious complication and the main reason for morbidity and mortality after pancreaticoduodenectomy (PD). Currently, there exists no flawless pancreaticojejunal anastomosis approach. We presents a new approach called Chen's penetrating-suture technique for pancreaticojejunostomy (PPJ), which involves end-to-side pancreaticojejunostomy by suture penetrating the full-thickness of the pancreas and jejunum, and evaluates its safety and efficacy. METHODS: To assess this new approach, between May 2006 and July 2018, 193 consecutive patients who accepted the new Chen's Penetrating-Suture technique after a PD were enrolled in this study. Postoperative morbidity and mortality were evaluated. RESULTS: All cases recovered well after PD. The median operative time was 256 (range 208-352) min, with a median time of 12 (range 8-25) min for performing pancreaticojejunostomy. Postoperative morbidity was 19.7% (38/193) and mortality was zero. The POPF rate was 4.7% (9/193) for Grade A, 1.0% (2/193) for Grade B, and no Grade C cases and one urinary tract infection. CONCLUSION: PPJ is a simple, safe, and reliable technique with ideal postoperative clinical results.

Inhibition of Gasdermin D blocks the formation of NETs and protects acute pancreatitis in mice.

The persistent activation of neutrophils and the excessive neutrophil extracellular traps (NETs) formation are the main determinants of pancreatic tissue injury and systemic inflammatory response in acute pancreatitis (AP). Thus, inhibiting the release of NETs can effectively prevent the aggravation of AP. Here, our study showed that the pore-forming protein gasdermin D (GSDMD) was activity in neutrophils of AP mice and patients and played the vital role in NETs formation. Through the application of GSDMD inhibitor or the construction of neutrophil GSDMD specific knockout mice, it was found in vivo and in vitro that inhibition of GSDMD could block the NETs formation, reduce pancreatic injury, systemic inflammatory reaction and organ failure in AP mice. To sum up, our findings confirmed that neutrophil GSDMD was the therapeutic target for improving the occurrence and development of AP.

CD36 accelerates the progression of hepatocellular carcinoma by promoting FAs absorption.

CD36 is emerging as a potential strategy for cancer treatment because of its function of regulating fatty acid intake. The purpose of this study was to clarify the molecular mechanism of CD36 in the progression of HCC. TCGA database was used to analyze the relationship of CD36 with HCC. The expression of CD36 in HCC clinical samples and cell lines was detected by qRT-PCR and western blot. Huh7 cells and HCCLM3 cells were transfected and treated into different group. CCK-8 and clone formation assay were used to detect the cell proliferation ability. Wound healing and transwell experiment were used to detect the metastatic ability. HCC xenografts were constructed in nude mice by subcutaneous injection of stably transfected Huh7 cells. The expression of CD36 in HCC was detected by immunohistochemistry (IHC). The contents of phospholipids and triglycerides in HCC cells were detected by ELISA. And the content of neutral lipids in HCC cells was detected by staining with BODIPY 493/503 and DAPI dye. Then transcriptional sequencing was used to determine the downstream mechanism of CD36 in HCC, and the differentially expressed genes (DEGs) were analyzed. CD36 was upregulated in HCC. Knockdown of CD36 could suppress the proliferation and metastasis of HCC in vitro and in vivo by regulating FAs intake in HCC. In addition, the expression of AKR1C2 was suppressed by sh-CD36, and which was also involved in the regulation of FAs intake. The molecular mechanism by which CD36 accelerated the progression of HCC was to promote the expression of AKR1C2 and thus enhance fatty acids (FAs) intake.

Corrigendum: The Ethyl Acetate Extract From Celastrus Orbiculatus Promotes Apoptosis of Gastric Cancer Cells Through Mitochondria Regulation by PHB.

[This corrects the article DOI: 10.3389/fphar.2021.635467.].

Inhibition of hypoxia-inducible factor-1α alleviates acinar cell necrosis in a mouse model of acute pancreatitis.

Hypoxia-inducible factor-1α (Hif1α) is activated in hypoxia and is closely related to oxidative stress, immunity and cell metabolism. Recently, it is reported that Hif1α is involved in atherosclerosis, ischemia-reperfusion (I/R) injury, alcoholic liver disease and pancreatic tumors. In this study, we found that Hif1 signal pathway is significantly changed in pancreas of acute pancreatitis (AP) mice. Meanwhile, we verified that the high expression of Hif1α injured pancreatic tissues of cerulean-induced AP mice, which prompting that Hif1α participated in the progress of histopathology on AP. We applied a Hif1α inhibitor PX478 and observed that it could alleviate histological injury of pancreas as well as the levels of serum amylase, lipase and proinflammatory cytokine in the murine model of AP induced by caerulein. In addition, PX478 could reduce the formation of necrosome (RIP3 and p-MLKL) and the generation of reactive oxygen species (ROS) in AP mice. Correspondingly, we further confirmed the effectiveness of PX478 in vitro and found that inhibiting Hif1α could mitigated the necrosis of pancreatic acinar cells via reducing the RIP3 and p-MLKL expression and the ROS production. In conclusion, inhibiting Hif1α could protect against acinar cells necrosis in AP, which may provide a new target for the prevention and treatment of AP clinically.

The Ethyl Acetate Extract From Celastrus orbiculatus Promotes Apoptosis of Gastric Cancer Cells Through Mitochondria Regulation by PHB.

Objective: To investigate the effect of ethyl acetate extract from Celastrus orbiculatus (COE) on gastric cancer cell apoptosis and reveal its underlying molecular mechanism. In addition, it was aimed to stablish a theoretical basis for the clinical application of Celastrus orbiculatus in the gastric cancer treatment. Material and Methods: Western blot and RT-qPCR were used to detect mRNA and protein expression of PHB in gastric cancer and adjacent tissues. MTT method was used to detect the COE effect on the proliferation of AGS cells and to determine the 50% inhibitory concentration COE on these cells. COE effect on AGS apoptosis was evaluated by flow cytometry. Changes in apoptosis-related proteins expression in AGS cells were detected by western blot and changes in mitochondrial membrane potential were detected by JC-1 fluorescence staining. PHB expression was knocked down in AGS cells by lentiviral-mediated RNA interference. The COE antitumor effect was assessed in vivo using a subcutaneous transplantation tumor model in nude mice and in vivo fluorescence tracing technique in small animals. Results: The clinical samples analysis results showed that the PHB expression in gastric cancer samples was significantly higher than in corresponding adjacent tissues. MTT results showed that the AGS cell proliferation was significantly inhibited. RT-qPCR and western blot results showed that COE can significantly inhibit the PHB mRNA and protein expression, respectively. Flow cytometry analysis showed that COE was able to significantly promote AGS cell apoptosis. Western blot results also indicated that apoptosis-related protein expression changed significantly; BCL-2 expression significantly reduced while the Caspase-3 and Bax expression significantly increased after COE treatment. JC-1 fluorescence staining results showed that COE changed the mitochondrial membrane potential and activated the mitochondrial apoptosis pathway. Furthermore, in vivo experiments results demonstrated that the growth of subcutaneous transplanted tumor was significantly inhibited by the PHB knockdown and by the COE intragastric administration. Conclusion: COE can significantly promote apoptosis of human gastric cancer cells, which can be achieved by inhibiting PHB expression, thus altering the structure and function of mitochondria and activating the mitochondria apoptosis pathway. The antitumor effect of COE has also been proved in vivo.

[Design and application of a retractable scalpel handle].

The scalpel is the most practical tool for surgeons. The traditional scalpel is a blade with a split handle, but the length of the blade cannot be adjusted, and it is easy to scratch medical staff. In order to solve the above problems, a retractable scalpel handle was designed by the medical staffs of department of general surgery, Affiliated Hospital of Yangzhou University (Clinical Teaching Hospital of Dalian Medical University), and obtained the National Utility Model Patent of China (ZL 2019 2 0203154.9). The telescopic scalpel adopted the design of rotary telescopic sleeve and threaded column handle to achieve the purpose of built-in blade. By rotating the handle at one end of the handle, the length of the surgical blade extending out of the sleeve could be adjusted according to the actual needs. The structure of the device is simple and easy to operate. The adjustable blade length could also achieve the purpose of accurate operation while effectively avoiding the injury of medical personnel during the operation.

Polypharmacological Profiles Underlying the Antitumor Property of Salvia miltiorrhiza Root (Danshen) Interfering with NOX-Dependent Neutrophil Extracellular Traps.

Danshen, the dried root of Salvia miltiorrhiza, one of the most investigated medicinal plants with well-defined phytochemical constituents, has shown prominent clinical outcomes for antioxidant, anti-inflammatory, and anticoagulant activities to attain vascular protection and additional benefits for cancer therapy. More recently, activation of neutrophil and excessive formation of neutrophil extracellular traps (NETs) have been observed in pathological conditions of metastatic cancers; thus, we hypothesized that suppression of NETs could account for an essential cellular event underlying Danshen-mediated reduction of the incidence of metastasis. Using an experimental pulmonary metastases model of red fluorescent protein- (RFP-) labeled gastric cancer cells in combination with macroscopic ex vivo live-imaging system, our data indicated that Danshen impaired the fluorescent intensity and quantity of metastatic nodules. Moreover, Danshen could prevent neutrophil trafficking to the metastatic sites with decreased plasma levels of neutrophil elastase (NE) and procoagulant potential featured by fibrinogen. We further established phorbol 12-myristate 13-acetate- (PMA-) induced NET formation of human neutrophils and screened representative active compounds derived from the hydrophilic and hydrophobic fractions of Danshen using qualitative and quantitative methods. As a result, we found that salvianolic acid B (Sal B) and 15,16-dihydrotanshinone I (DHT I) exhibited superior inhibitory activities on NET formation and significantly attenuated the levels of citrullinated histone H3 (citH3), a biomarker for NET formation. Multitarget biochemical assays demonstrated that Sal B and DHT I distinctly modulated the enzymatic cascade involved in NET formation. Sal B and DHT I could disrupt NET formation at the earlier stage by blocking the activities of myeloperoxidase (MPO) and NADPH oxidase (NOX), respectively. Lastly, combining treatment of Sal B and DHT I under subED50 doses displayed remarkable synergism effect on NET inhibition. Altogether, these data provide insight into how promiscuous compounds from herbal medicine can be effectively targeted NETs towards hematogenous metastasis of certain tumors.

Anticancer efficacy of the ethyl acetate extract from the traditional Chinese medicine herb Celastrus orbiculatus against human gastric cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) herb Celastrus orbiculatus is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. The ethyl acetate extract of C. orbiculatus (C. orbiculatus extract, COE) was reported to show significant antitumor effects. However, no study in China or abroad has reported the effect and mechanism of COE in triggering apoptosis of gastric cancer (GC) cells. AIM OF STUDY: To further uncover the molecular mechanism underlying COE's apoptotic and anti-proliferative effects and lay a foundation for the development of novel, effective antitumor TCM agents. MATERIALS AND METHODS: The effect of COE on AGS and BGC-823 GC cell viability was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of AGS and BGC-823 cells induced by COE was analyzed using flow cytometry and a mitochondrial membrane potential assay kit (JC-1). The proliferating GC cells were identified and examined using a 5-bromo-2'-deoxyuridine (BrdU) staining kit and flow cytometric analysis. A western blot assay was used to detect the effect of COE on apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2), Bcl-extra-large (Bcl-xL), Bcl-2-like protein 12 (Bcl-L12), Bcl-2-associated X protein (Bax), and caspase as well as proliferation-related proteins, phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)/p70s6k. Transmission electron microscopy (TEM) and an animal imaging technique were used to evaluate the microstructure of apoptotic GC cells and the effect of COE on tumor cell growth in vivo, respectively. RESULTS: The results indicate that COE significantly inhibited proliferation and induced apoptosis of GC AGS and BGC-823 cell lines both in vivo and in vitro. COE significantly decreased the cell mitochondrial membrane potential. Moreover, COE downregulated the levels of Bcl-2, Bcl-xL, and PI3K/Akt/mTOR/p70s6k while those of Bax and caspase were upregulated. More interestingly, COE altered the microstructure of the mitochondria. CONCLUSION: All these data collectively indicate that COE not only has significant antiproliferative effects but also has both in vivo and in vitro apoptotic effects. In addition, COE altered the structure and function of the mitochondria, which is another potential pathway for the antitumor activity of COE. These findings may provide a basis for the development of new anticancer TCM candidates.

Cofilin 1 induces the epithelial-mesenchymal transition of gastric cancer cells by promoting cytoskeletal rearrangement.

Epithelial-mesenchymal transition (EMT) is an important biological process whereby malignant tumor cells obtain the ability to migrate, invade, resist apoptosis and degrade the extracellular matrix. We found that Cofilin1 (CFL1) expression was elevated in clinical gastric cancer specimens and correlated with biomarkers of EMT in BGC-823 gastric cancer cells. BGC-823 cells exhibited EMT phenotypes and increased metastatic ability when induced by TGF-ß1. By contrast, BGC-823 cells transfected with Lv-siRNA-CFL1 did not exhibit EMT phenotypes under the same inducing conditions. As CFL1 expression increased, EMT cell filopodia stretched out. In addition, the ultrastructures observed using transmission electron microscopy indicated that silencing of CFL1 markedly inhibited depolymerization of fibrous actin and cytoskeletal reorganization during EMT. Similar results were obtained in vivo. These findings demonstrate that CFL1 induces EMT by promoting cytoskeletal rearrangement. Our results may provide the basis for developing new anticancer drugs to inhibit CFL1.

Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats.

The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF­κBp65 expression levels, with reduced expression of Bcl­2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF­α and IL­1 were significantly reduced in the IP group. Immunohistochemistry for Bcl­2 and Bax indicated that Bcl­2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro­inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury.

Clinicopathological Significance of MicroRNA-20b Expression in Hepatocellular Carcinoma and Regulation of HIF-1α and VEGF Effect on Cell Biological Behaviour.

miRNA-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miRNA-20b in the prognosis of patients with hepatocellular carcinoma (HCC) is poorly understood, and the exact role of miRNA-20b in HCC remains unclear. The aim of the present study was to investigate the association of the expression of miR-20b with clinicopathological characteristics and overall survival of HCC patients analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. Meanwhile, the HIF-1α and VEGF targets of miR-20b have been confirmed. We found not only miR-20b regulation of HIF-1α and VEGF in normal but also regulation of miR-20b in hypoxia. This mechanism would help the tumor cells adapt to the different environments thus promoting the tumor invasion and development. The whole study suggests that miR-20b, HIF-1α, and VEGF serve as a potential therapeutic agent for hepatocellular carcinoma.

miR-20b overexpression is predictive of poor prognosis in gastric cancer.

BACKGROUND: miR-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miR-20b in the prognosis of patients with gastric cancer (GC) is poorly understood, and the exact role of miR-20b in GC remains unclear. MATERIALS AND METHODS: The expression of miR-20b was detected in 102 patients with GC by a SYBR Green assay and was compared with the expression in matched adjacent normal tissue specimens. The aim of the present study was to investigate the association of the expression of miR-20b with the clinicopathological characteristics and the overall survival of patients with GC as analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. RESULTS: Our results showed that miR-20b expression was upregulated in GC tissue compared with normal mucosa (P=0.00). Furthermore, miR-20b expression was positively correlated with advanced lymph node metastasis (P=0.041), tumor node metastasis stage (P=0.000), and deeper and distant metastasis (P=0.031). The overall survival rate of patients with GC was significantly lower in those whose tumors expressed high levels of miR-20b mRNA compared with those whose tumors expressed low levels of miR-20b mRNA (P=0.019). CONCLUSION: miR-20b may serve as a potential molecular marker for the prognosis of GC.

Mesh erosion causes small bowel obstruction: a rare complication of laparoscopic inguinal hernia repair: case description and review of literature.

Transabdominal preperitoneal (TAPP) and total extraperitoneal (TEP) are the two types of laparoscopic repair of the inguinal hernia. The main advantages of laparoscopic repair, as compared to open repair, are a shorter hospital stay and a quicker recovery to normal activities. However, we cannot be overlooked or neglected the complication of laparoscopic inguinal hernia repair although it brings us lots of benefits. We report a case of small bowel obstruction caused by a displaced mesh used for the laparoscopic inguinal hernia repair and review of literature.

Impact of hypoxic preconditioning on apoptosis and its possible mechanism in orthotopic liver autotransplantation in rats.

BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P<0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P<0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P<0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.