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To explore the analgesic effect of dizocine combined with ropivacaine on recurrent neuropathic pain in rat model of peripheral nerve compression. Rats were randomly divided into 5 groups: sham control group (S), peripheral nerve compression model group (M), dizocine group (D), ropivacaine group (R), and combined drug group (DR). Rat peripheral nerve compression model was constructed to observe the symptoms of the rats before and after surgery. Mechanical withdrawal threshold was measured on the 21st day after surgery. The electrophysiological changes of rat peripheral nerve were measured by biopotential recording system, including proximal latency, distal latency, and compound muscle action potential. The incubation period and nerve conduction velocity were further obtained. Histological changes were observed by HE staining and toluidine blue staining. Axon number and myelin damage grade were performed, and the ultrastructure was observed by transmission electron microscopy (TEM). The mechanical withdrawal threshold, nerve conduction velocity, and compound muscle action potential were effectively increased in combination group. However, the proximal latency, distal latency, and incubation period were significantly reduced. Furthermore, dizocine combined with ropivacaine can effectively reduce the degree of myelination. TEM shown that the DR group had the best therapeutic effect, and the histological appearance of the cross section was quite similar to that of the S group. Dizocine combined with ropivacaine has a significant analgesic effect in rat model of peripheral nerve compression. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare the expression of transcriptional coactivator with the PDZ-binding motif (TAZ) in pancreatic cancer (PC) patients, and to investigate the regulation mechanisms of TAZ in the proliferation of PC. PC tissues and matched peritumoral tissues, pancreatic juice and serum were collected from PC patients who underwent pancreatectomy between June 2012 and December 2015 at the Affiliated Hospital of Qingdao University (Qingdao, China). Pancreatic juice and serum were collected from patients with chronic pancreatitis as a control. The levels of taz mRNA expression in the samples were examined by reverse-transcription quantitative polymerase chain reaction, and the protein expression of TAZ was assessed by western blot analysis and ELISA. MicroRNAs (miRNAs) that regulate TAZ expression were also predicted by bioinformatics analysis and validated by dual luciferase reporter and rescue assays. In addition, the proliferation of PC cells was evaluated after transfection with TAZ small interfering RNA (siRNA) or its upstream miRNA agomir. Expression of TAZ was significantly increased in the PC tissues, pancreatic juice and serum of PC patients at the mRNA and protein levels compared with controls (P<0.05). Furthermore, TAZ was predicted and verified to be a target of miRNA (miR)-185, and miR-185 and TAZ were inversely expressed in samples from PC patients (P<0.05). In addition, TAZ siRNA or agomiR-185 transfection significantly inhibited human pancreatic adenocarcinoma cell proliferation (P<0.05). However, overexpression of TAZ in the agomiR-185 group rescued the inhibition (P<0.05). Finally, the expression of TAZ effector proteins, namely ankyrin repeat domain-containing protein and cysteine-rich 61, were upregulated in PC tissues (P<0.05), but repressed following transfection of PC cells with agomiR-185 (P<0.05). Thus, miR-185 may regulate the proliferation of PC by targeting TAZ, making it a promising diagnostic marker for PC. [ABSTRACT FROM AUTHOR]

Although the understanding of sepsis has evolved from "sepsis 1.0" to "sepsis 3.0", and the consensus on clinical management of sepsis has been continuously updated, the incidence rate and mortality of sepsis remain high. Therefore, in-depth investigation of the pathogenesis and related influencing factors of sepsis is of great significance for revealing the nature of sepsis and improving the clinical outcome of sepsis patients. This review will focus on the key issues in the basic research of sepsis, and summarize the recent advances and challenges in this field, mainly including genetic polymorphism, microorganisms, high-mobility group box 1 (HMGB1), endothelial dysfunction, immunotherapy, and biomarkers, aiming to provide new insights for the diagnosis and treatment of sepsis.

Objective: Inflammation and oxidative stress contribute to the progression of sepsis-induced acute lung injury (ALI). SAM domain, SH3 domain and nuclear localization signals 1 (SAMSN1) is a signaling adaptor protein, and mainly regulates inflammatory response of various immune cells. The present study generates macrophage-specific SAMSN1-knockout (Samsn1 MKO ) and SAMSN1-transgenic (Samsn1 MTG ) mice to investigate its role and mechanism in sepsis-induced ALI., Methods: Samsn1 MKO and Samsn1 MTG mice were exposed to lipopolysaccharide (LPS) instillation or cecal ligation and puncture (CLP) surgery to induce sepsis-induced ALI. Bone marrow transplantation, cellular depletion and non-invasive adoptive transfer of bone marrow-derived macrophages (BMDMs) were performed to validate the role of macrophage SAMSN1 in sepsis-induced ALI in vivo. Meanwhile, BMDMs were isolated from Samsn1 MKO or Samsn1 MTG mice to further clarify the role of SAMSN1 in vitro., Results: Macrophage SAMSN1 expression was increased in response to LPS stimulation, and negatively correlated with LPS-induced ALI in mice. Macrophage SAMSN1 deficiency exacerbated, while macrophage SAMSN1 overexpression ameliorated LPS-induced inflammation, oxidative stress and ALI in mice and in BMDMs. Mechanistically, we found that macrophage SAMSN1 overexpression prevented LPS-induced ALI though activating AMP-activated protein kinase α2 (AMPKα2) in vivo and in vitro. Further studies revealed that SAMSN1 directly bound to growth factor receptor bound protein 2-associated protein 1 (GAB1) to prevent its protein degradation, and subsequently enhanced protein kinase A (PKA)/AMPKα2 activation in a protein tyrosine phosphatase, non-receptor type 11 (PTPN11, also known as SHP2)-dependent manner. Moreover, we observed that macrophage SAMSN1 overexpression diminished CLP-induced ALI in mice., Conclusion: Our study documents the protective role of macrophage SAMSN1 against sepsis-induced inflammation, oxidative stress and ALI through activating AMPKα2 in a GAB1/SHP2/PKA pathway, and defines it as a promising biomarker and therapeutic target to treat sepsis-induced ALI., Competing Interests: Declaration of competing interest The authors report no potential conflicts of interest in this work., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Neuroendocrine tumors of the ureter are extremely rare. There are only a few case reports in the past decades. Their clinicopathologic features, therapy and prognosis are not that clear., Methods: 5 cases of ureteral neuroendocrine tumors were collected and reviewed of the literature. Histomorphology, immunophenotype and ultrastructural features were observed by HE, immunohistochemistry, special staining and electron microscopy. The clinical pathological data were retrospectively analyzed and followed up., Results: Among the 5 patients, 1 was female and 4 were male, aged 62-82 years. 2 cases manifested intermittent hematuria, 1 had lower abdominal pain with frequent urination and dysuria, 1 with hydronephrosis, and 1 had no manifestations. All the 5 patients were treated with nephroureterectomy, 3 of which were also treated with excision of bladder cuff, 1 also had lymphadenectomy. On presentation, 2 cases in T2N0M0 (stage II), 2 cases in T3N0M0 (stage III), and 1case in T3N2M0 (stage IV). 2 cases were small cell neuroendocrine carcinoma, 1 was large cell neuroendocrine carcinoma and 2 were atypical carcinoid. The tumor cells were positive for neuroendocrine markers (CD56, CgA, Syn). 1 case of vimentin-positive small cell neuroendocrine carcinoma has a very good prognosis. Grimelius stain and electron microscopy observation showed numerous neuroendocrine granules in the cytoplasm., Conclusion: Ureteral neuroendocrine tumors are extremely rare. Neuroendocrine markers (CD56, CgA, Syn) and epithelial markers (CKpan, CK7) are usually helpful. Grimelius special staining and electron microscopy observation can help to make a final diagnosis. Radical surgery together with postoperative adjuvant chemotherapy can improve the survival of patients. Vimentin may play a role in predicting the prognosis., Competing Interests: Declaration of Competing Interest There are no conflicts of interests to declare., (Copyright © 2019 Elsevier GmbH. All rights reserved.)