Objective:To investigate the effect of high-dose vitamin B6 on stress-induced liver cell death in rats with severe trauma and its possible mechanism.Methods:Thirty-two male SD rats were selected and divided into sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group by using a random number table, with 8 rats in each group. Rat models of severe trauma were established by inducing abdominal wall injury, bilateral femoral fractures, unilateral cranial injury, and withdrawal of 4 ml blood from the femoral artery. The sham surgery+B6 group and trauma+B6 group were treated with saline solution plus high-dose vitamin B6, while the sham surgery group and trauma group with infusion of saline solution only. At 36 hours after injury, rat liver tissues were collected for the following experiments: (1) the genes differentially expressed in the liver tissues of the rats of the trauma group and the trauma+B6 group were screened with next-generation sequencing, followed by an analysis of the possible involvement of cell death pathways; (2) validation was conducted to ascertain whether high-dose vitamin B6 could influence various cell death pathways in the liver cells in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group: apoptosis was confirmed through terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining; necroptosis was verified by mixed lineage kinase domain-like protein (MLKL) immunohistochemical staining; autophagy was examined via transmission electron microscopy; ferroptosis was confirmed by detecting oxidative malondialdehyde (MDA) levels, oxidized glutathione levels, Prussian blue staining with diaminobenzidine (DAB) enhancement, transmission electron microscopy, and immunohistochemical staining for acyl-CoA synthetase long-chain family member 4 (ACSL4); (3) Biological information analyses [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Enrichment analysis (GSEA)] were performed for biological processes and signaling pathways represented by liver tissue sequencing results of rats between the trauma group and the trauma+B6 group.Results:(1) In the liver tissues of rats, there were 344 significantly differentially expressed genes between the trauma group and trauma+B6 group, comprising 137 upregulated genes and 207 downregulated genes, of which 18 genes were associated with apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. (2) No significant differences were found in TUNEL staining among the sham surgery group, sham surgery+B6 group, trauma group or trauma+B6 group; MLKL protein expression levels in the liver tissues after trauma were improved, of which the trauma+B6 group was lower than that of the trauma group; Electron microscopy showed that autophagic activity in the liver cells were significantly increased after trauma, which was significantly lower of the trauma+B6 group than that of the trauma group; MDA levels in the rat liver tissues were (0.20±0.05)nmol/mg, (0.17±0.07)nmol/mg, (0.69±0.11)nmol/mg and (0.52±0.07)nmol/mg in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group respectively ( P<0.01), with the trauma group having the highest MDA levels and trauma+B6 group having lower MDA levels than the trauma group; Oxidized glutathione levels in the liver tissues of the four groups were (11.75±2.09)μmol/g, (11.69±1.66)μmol/g, (19.75±3.40)μmol/g, and (14.51±1.46)μmol/g respectively ( P<0.01), with the trauma group having the highest levels and trauma+B6 group having lower levels than the trauma group; Significantly increased iron deposition was observed in the liver tissues after trauma, with lower iron deposition in trauma+B6 group than the trauma group; Electron microscopy revealed significantly lower mitochondrial membrane density in the trauma+B6 group compared to the trauma group. ACSL4 protein expression level was lower in the trauma+B6 group compared to the trauma group; (3) GO, KEGG and GSEA enrichment analyses suggested that high-dose vitamin B6 may enhance cholesterol synthesis metabolism in the liver cells and alleviate oxidative stress to reduce liver cell damage and restore normal liver cell function after trauma. Conclusions:High-dose vitamin B6 attenuates stress-induced liver injury in rats with severe trauma by inhibiting the progression of necroptosis, autophagy and ferroptosis. Its molecular mechanism may be associated with enhanced hepatic cholesterol synthesis metabolism and alleviation of oxidative stress in the liver cells.

ObjectiveTo establish a rat model of diabetic wound by feeding on a high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin （STZ） and surgical preparation of full-thickness skin defects， observe the effect of cinnamaldehyde on the wound healing of diabetes rats， and explore the therapeutic mechanism of cinnamaldehyde in improving wound healing of diabetes rats based on the PTEN-induced putative kinase （PINK1）/Parkin pathway-mediated mitochondrial autophagy. MethodForty-eight male SD rats were randomly divided into blank group （n=12） and diabetes group （n=36）. The diabetes group was further randomly divided into model group， cinnamaldehyde group， and Beifuxin group， with 12 rats in each group. The blank group and the model group received routine disinfection with physiological saline after creating the wounds， while the cinnamaldehyde group received topical application of polyethylene glycol 400 （PEG 400） gel containing 4 μmol·L^-1 cinnamaldehyde， and the Beifuxin group received topical application of Beifuxin gel. Dressings were changed once daily. The wound healing rate of each group was observed. On the 7th and 14th days after intervention， the wound tissues of the rats were collected. Hematoxylin and eosin （HE） staining was performed to observe the pathological changes in the local tissues. Immunohistochemistry （IHC） was used to detect the expression of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， vascular endothelial growth factor （VEGF）， and collagen fibers. Immunofluorescence （IF） and Real-time polymerase chain reaction （Real-time PCR） were used to detect the protein， and mRNA expression of PINK1， Parkin， microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. ResultAfter intraperitoneal injection of STZ， compared with the blank group， the random blood glucose values of rats in the diabetic group increased significantly （P<0.01）， all higher than 16.7 mmol·L^-1， and persistently hyperglycemic for some time after modeling. Compared with the blank group， the model group showed poor growth and healing of granulation tissue in the wounds， and the wound healing rate decreased （P<0.01）. On the 7^th day after intervention， the blank group had squamous epithelial coverage on the wounds. Compared with the blank group， the model group only had a small amount of scab at the wound edges， with a large number of infiltrating inflammatory cells in the wounds. The protein expression levels of IL-6 and TNF-α in the tissues increased （P<0.01）， and the protein and mRNA levels of PINK1， Parkin， and LC3Ⅱ decreased （P<0.01）. On the 14^th day after the intervention， the granulation tissue in the wounds of the blank group was mature and well-healed. Compared with the blank group， the model group still had infiltrating inflammatory cells and red blood cell exudation. The protein expression levels of VEGF and collagen fibers in the tissues decreased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ increased （P<0.01）. Compared with the model group， the cinnamaldehyde group and the Beifuxin group showed better wound healing， with increased wound healing rates （P<0.01）. On the 7th day after intervention， the protein expression levels of IL-6 and TNF-α in the tissues decreased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ increased （P<0.01）. On the 14th day after intervention， the protein expression levels of VEGF and collagen fibers in the tissues increased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ decreased （P<0.01）. ConclusionCinnamaldehyde can promote the wound healing of diabetes rats by increasing the wound healing rate， reducing the levels of inflammatory factors IL-6 and TNF-α， and increasing the levels of VEGF and collagen fibers. Its mechanism may be related to the regulation of the PINK1/Parkin signaling pathway， activation of mitochondrial autophagy， inhibition of inflammatory responses， and promotion of angiogenesis and collagen synthesis， thereby promoting the wound healing of diabetes rats.

Objective:To investigate the effect of Astragaloside Ⅳ-mediated Endothelial progenitor cells derived exosomes (EPC-Exos) on the biological function of EPC-Exos damaged by high glicose.Methods:EPCs from human umbilical cord blood were isolated and cultured in vitro. the EPC-Exos secreted by EPCs were extracted by ultracentrifugation combined with ultrafiltration, and identified by specific markers CD9, CD63 and CD81, respectively. After the cells were cultured for 24 hours with AS-IV at 100 mg/L and PBS at the same volume, the morphological characteristics of EPC-Exos were observed by transmission electron microscope. Human endothelial cells were isolated, cultured and identified in vitro. The identified endothelial cells were pretreated with 30 mmol/L glucose for 120 h and randomly divided into experimental group and control group, at the same time set the normal group. The cells were cultured for 24 hours, the effects of EPC-Exos on proliferation, adhesion, migration and angiogenesis of endothelial cells damaged by high glucose were observed by using cell counting kit-8 (CCK-8) Cell Proliferation Assay Kit, cell scratch test, adhesion assay and in vitro angiogenesis assay by Matrigel. Results:Compared with the normal group, the proliferation, migration, adhesion and tubulogenesis of human endothelial cells in the control group were significantly lower ( t=24.35, 6.80, 10.65, 9.62, P<0.05). Compared with the control group, the proliferation, adhesion, migration and tubulogenesis of human endothelial cells in the experimental group were significantly enhanced ( t=30.68, 5.99, 5.40, 8.25, P<0.05). Conclusions:EPC-Exos mediated by AS-Ⅳ can significantly improve the biological function of human endothelial cells damaged by high glucose and has the potential to modulate endothelial neovascularization in diabetic rats.

Objective:To construct a three-dimensional imaging model of the pancreatic head based on the embryological fusion plane, and to provide morphological parameters of the pancreatic head for future developments of basic and clinical researches on the pancreas.Methods:Histologic cross-sections of the pancreatic head with its adjacent structures were made from healthy cadavers. Immunohistochemical analysis of pancreatic polypeptide antibody was then performed to verify the existence and location of the embryological fusion plane reported previously. The histologically positioning method of the embryological fusion plane was then applied to the corresponding sections on computed tomography (CT). Based on the results of the above work, volunteers from the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University were then used as research objects. A three-dimensional visualization reconstruction software was used to perform CT image-based structures to include the abdominal pancreas, dorsal pancreas head, and embryo fusion surface. Three-dimensional reconstruction of the pancreatic head, and morphological measurements of the relevant structures of the pancreatic head were then made.Results:Immunohistochemical analysis verified the existence and the position of the embryological fusion plane. The histologically positioning method was then successfully applied to the CT sections. The three-dimensional imaging model of the pancreatic head containing the embryological fusion plane, dorsal segment and ventral segment of head were built based on CT images. A total of 35 volunteers were included, including 19 males and 16 females, aged (48.26±8.26) years, and with a BMI of (22.29±1.78) kg/m 2. The morphological results showed that the volume of the pancreatic head, dorsal pancreas and abdominal pancreas were (32.80±8.15) cm 3, (22.21±6.94) cm 3, (10.59±3.87) cm 3, and the area of the embryo fusion surface was (12.46±3.20) cm 2. All volunteers were then grouped according to gender. Statistical analysis showed that there were no significant differences in the total pancreatic head volume, dorsal pancreatic head volume, abdominal pancreatic volume, and embryo fusion area among the groups ( P>0.05). Conclusions:It was feasible and practical to build a three-dimensional imaging model of the pancreatic head based on the embryological fusion plane by using a 3D computer system. This model and its morphological parameters could provide a new tool for research on pancreas.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective To assess the safety and effectiveness of yttrium-90 (90Y) radioembolization for patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT).Methods The PubMed was searched for all clinical reports from 1991 to 2017.Results A total of 17 clinical studies including 662 patients were qualified for the analysis.The median time to progression was 5.8 months,and median disease control rate was 68.4％.The median survival was 10 months in all patients,including the median OS of 13.8,6.5 months of Child-Pugh class A and B patients,respectively,the median OS were 13.4,5.4 months respectively in branch and main PVTT patients,and the median OS were 3.7,9.5 months of patients who received resin and glass based microspheres,respectively.The median radioembolization induced liver disease was 36.3％.The median abdominal pain,nausea/vomiting,fatigue,and fever were 18.8％,17.6％,11.1％,and 1.4％.Conclusion 90y radioembolization is an effective treatment for HCC and PVTT,which is an alternative treatment choice for HCC and PVTT.

Pancreas arises from dorsal and ventral anlagen,and there is an embryological fusion plane between them.The embryological fusion plane can be discriminated by immunohistochemical staining for an anti-pancreatic polypeptide or computed tomography.The embryological fusion plane can not only guide the management of benign or low malignant potential tumors,but also determine the clinicopathological characteristics of pancreatic head cancer and patients'survival,and the embryological fusion plane plays an important role in the management of pancreatic disease.In this review,the research progressions and clinical significance in the embryological fusion plane of dorsal and ventral pancreas are described.

Three dimensional (3D) imaging and 3D printing have been applied in pancreatic malignancy management.The 3D imaging can not only be applied in pre-procedural evaluation and planning,but also it can be used for residents and fellows for training and education,and families of patients advsing.A model of pancreatic and its surrounding structures can be gotten by the 3D printing technique based on 3D imaging,which can not only recognize the anatomical structure,but also can make the guidance for the procedure.3D imaging and 3D printing technique have an important role in the management of pancreatic malignancy.In this review,we summarized the application of 3D) imaging and 3D printing in malignant neoplasm of pancreas.

Pancreas arises from dorsal and ventral anlagens on an embryological basis,with a difference in histocytology.Immunohistochemical staining for an anti-pancreatic polypeptide can be performed to discriminate between the dorsal and ventral pancreas because of the difference in the amount of pancreatic polypeptide contained by the dorsal and ventral pancreas.Differences of survival in patients were approved due to the difference in histocytology between the dorsal and ventral pancreas,including the ability of local invasion,lymph node metastases,and nerve plexus invasion.

Colorectal liver metastasis (CRLM) is a common liver metastatic tumor with poor prognosis.It was very difficult to treat patients with unresectable and chemotherapytolerant CRLM.With the tumor control rate ranging from 63％ to 78％,Yttrium-90 is both safe and effective in treating unresectable and chemotherapy-tolerant CRLM.The median survival time is 10.5 months,and the 1-,2-,3-year overall survival rates of patients are 44％,20％ and 14％ respectively.For a certain portion of patients,Yttrium-90 has distinct advantages over mo lecular targeted drugs and other local minimally invasive treatment.Though Yttrium-90 treatment has showed certain curative effect,its safety and effectiveness require further confirmation through multi-center randomized controlled trial.