Objective To validate the mechanism of effect of hepatic artery ischemia on biliary fibrosis after liver transplantation and the prevention method. Methods Eighteen male dogs were established into the concise auto orthotopic liver transplantation models and assigned into three groups randomly: hepatic artery ischemia (HAI) group, TBB group (transferred the blood by a bridge duct ) and control group, each group contained 6 dogs. After opening portal vein, the samples were cut from liver in each group at the time of 6 h, 3 d and 14 d. The pathological modifications of intrahepatic bile ducts were observed and expression of transforming growth factor-β1 (TGF-β1) were detected in the three times. Expressions of Smad3 and phosphate-Smad3 as well as mRNA of α-smooth muscle actin (α-SMA) in intrahepatic bile ducts were detected 14 d after opening portal vein.Results Compared with control group, the collagen deposition and lumens stenosis in biliary vessel wall were more obviously in HAI group. In TBB group, the pathological modifications were slighter compared with HAI group. The positive cell index of TGF-β1 reached peak on day 3 after opening portal vein, then decreased in TBB group, and which in HAI group kept increase and was significantly higher than that in TBB group （Plt;0.05）. The expression level of phosphate-Smad3 and transcriptional level of α-SMA mRNA were 1.04±0.13 and 1.12±0.55 in TBB group on day 14 after opening portal vein, which were significantly higher than those in control group (0.59±0.09 and 0.46±0.18) and lower than those in HAI group (1.82±0.18 and 1.86±0.73), the diversities among three groups were significant (Plt;0.05). There was not significant difference of expression of Smads among three groups (Pgt;0.05). Conclusions Hepatic artery ischemia could increase the deposition of collagen fibers and the transdifferentiation of myofibroblast in bile duct and result in the biliary fibrosis by activating the TGF-β1/Smads signaling pathway. The bridging bypass device could lessen the biliary fibrosis caused by hepatic artery ischemia by inhibiting the activation of TGF-β1/Smads signal transduction passageway.
ObjectiveTo investigate the expressions of contactin-1 (CNTN-1), vascular endothelial growth factor-C (VEGF-C), and its receptor VEGFR-3 (Flt-4) in primary gastric cancer and to explore the relevance among them and their correlation with clinicopathologic features of gastric cancer. MethodsThe VEGF-C, VEGFR-3, and CNTN-1 protein expressions of tumor tissues and normal gastric mucosa tissues in 68 patients with primary gastric cancer were analyzed by immunohistochemistry. The Flt-4-positive vessel density (FVD) and lymphatic vessel density (LVD) were also analyzed by VEGFR-3positive and D2-40-positive staining, respectively. ResultsThe positivity rate of VEGF-C, VEGFR-3, and CNTN-1 protein expression in the primary tumor was 57.4% (39/68), 60.3% (41/68), and 55.9% (38/68), respectively, which was significantly higher than that in the normal gastric mucosa tissues 〔20.6% (14/68), 23.5% (16/68), and 16.2% (11/68)〕， P=0.000. The expressions of VEGF-C, VEGFR-3, and CNTN-1 protein were significantly correlated with TNM stage, lymphatic vessel invasion, and lymph node metastasis (Plt;0.05). The expression of CNTN-1 protein was significantly correlated with VEGF-C (r=0.372, P=0.002) and VEGFR-3 protein expression (r=0.308, P=0.011). In tumor tissues of sixtyeight patients the FVD was (10.41±9.38)/HP, which was significantly lower than LVD 〔(18.19±7.44)/HP〕, P=0.000. Elevated FVD and LVD was significantly found in patients with tumor characterized by later TNM stage, severer lymphatic vessel invasion, and severer lymph node metastasis (Plt;0.05). The FVD of tumor was significantly correlated with VEGF-C (P=0.029) and CNTN-1 protein expression (P=0.003). The LVD of tumor was not significantly correlated with CNTN-1 (P=0.727), VEGF-C (P=0.173), and VEGFR-3 protein expression (P=0.924). The patients with positive expression of VEGF-C, VEGFR-3, and CNTN-1 protein showed poorer prognosis (Plt;0.05). ConclusionsElevated expression of CNTN-1 protein is observed in primary gastric cancer and correlated with VEGF-C and VEGFR-3 protein expression, indicating that combined detection has great value in prediction of invasive potential and prognosis. VEGF-C-mediated CNTN-1 overexpression may promote lymphatic invasion via lymphangiogenesis pathway in patients with gastric cancer.
Objective PIWI-interacting RNA (piRNA) has emerged as a promising tool for cancer diagnosis. The aim of this meta-analysis was to summarize the existing literature and systematically assess the diagnostic performance of piRNAs in cancer, as well as identify potential sources of inter-study heterogeneity to provide information for clinical practice. MethodsThe PubMed, Web of Science, Embase, Cochrane library, CNKI, WanFang, VIP and CBM databases were electronically searched to collect diagnostic trials of piRNAs in cancer from inception to April 2023. The methodological quality of the included studies was assessed using the QUADAS-2 tool, and statistical analysis was conducted using Stata 17.0 software. ResultsA total of 17 papers (46 studies) involving 4 956 cancer patients and 3 759 controls were included. The range of sensitivity was 21%-100% and the range of specificity was 50%-100%. Meta-analysis showed that the combined sensitivity of piRNA for the diagnosis of cancer was 0.74 (95%CI 0.68 to 0.79), the specificity was 0.79 (95%CI 0.75 to 0.82), the PLR was 3.49 (95%CI 3.01 to 4.05), the NLR was 0.33 (95%CI 0.27 to 0.40), DOR of 11 (95%CI 8 to 14), and AUC of 0.83 (95%CI 0.80 to 0.86), indicating that piRNA had high accuracy for cancer diagnosis. Conclusion piRNA shows promise as a reliable biomarker for cancer diagnosis, with good sensitivity and specificity. However, the lack of standardization and result reproducibility remain significant challenges in the clinical application of piRNA-based diagnostics.
Objective To measure the expression level of Myc-interacting zinc finger protein-1 (MIZ1) in peripheral blood mononuclear cells (PBMC) of patients with severe and non-severe community-acquired pneumonia (CAP) and its relationship with inflammatory factors. Methods Thirty-six CAP patients from Beijing Chaoyang Hospital from April 2018 to June 2019 were enrolled in this study. MIZ1 mRNA level in PBMC were measured by reverse transcriptase-quantitative polymerase chain reaction. The levels of interleukin (IL)-6, IL-8, IL-10, and interferon-α in the serum of patients were measured by enzyme-linked immunosorbent assay. The levels of MIZ1 mRNA and inflammatory factors were compared between the severe CAP patients and the non-severe CAP patients. Results Compared with non-severe CAP patients, the MIZ1 mRNA level in the PBMC of severe CAP patients was lower (P<0.05) than non-severe group. Receiver operating characteristic (ROC) curve of the expression level of MIZ1 in PBMC was calculated according to whether CAP was severe or non-severe, and the area under ROC curve was 0.731 (P=0.018). Spearman correlation analysis showed that MIZ1 mRNA was negatively correlated with IL-10 level in the severe CAP patients (Spearman correlation co-efficient was –0.620, P<0.05). Conclusions MIZ1 may indicate the severity of CAP. MIZ1 may affect IL-10 so as to play a role in inflammation regulation.
Objective Through studying a diabetic patient accompanied with pancreatic cancer by means of evidence-based clinical practice, to find out the relationship between diabetes mellitus and cancer and whether the long-acting insulin glargine increases the risk of cancer or not, which is regarded as a disputable hot issue at present. Methods Such databases as The Cochrane Library (Issue 3, 2010), OVID-EBM Reviews (1991 to Sept. 2010), MEDLINE (1950 to Sept. 2010) and CNKI (2000 to Sept. 2010) were retrieved to collect high quality clinical evidence, and the best therapy was formulated in accordance with the willingness of patients themselves. Results Eight randomized controlled trials (RCTs), four meta-analyses and one RCT meta-analysis were included. The evidence indicated that: a) Diabetes mellitus was kind of related to the occurrence of malignancies; b) There was no evidence at present showing the relationship between long-acting insulin glargine and cancer; c) Strictly controlling of blood sugar did not increase the risk of tumorigenesis, but hyperglycemia causing cancer was proofless; and d) Whether the diabetic patient with cancer should stop taking long-acting insulin glargine or not should require suggestions from specialists rather than patients themselves. Conclusion No evidence at present shows that tumorigenesis is related to diabetes mellitus, long-acting insulin glargine and strict controlling of blood sugar. It is necessary to require more evidence to decide whether the therapy should be adjusted or not for the diabetic patient with cancer who is in the process of glargine therapy.
ObjectiveTo investigate the mechanism of impeded wound healing by exogenous hyaluronan (HA). Methods Wound healing models were established on 18 adult rabbit ears, which were randomly divided into 3 groups, the 2% HA treated-group (group A), the 1% HA treated-group(group B), and the PBS control-group (group C). The process of wound healing was observed morphologically and histologically. The expression of α-smooth muscle actin in fibroblast was measured by immunohistochemical method. Results ①The mean values of wound healing time of groups A, B and C were (11.7±0.6), (11.3±0.6), and (10.8±1.0) days respectively. Wound contraction was greater in group C than in group A and group B. ②Compared with PBS controls, the collagen fibril was slender and arrayed regularly in HA treated wound. ③ The expression of α-smooth muscle actin was greater in group C than in groups A and B. Conclusion It is one of reasons of impeded wound healing that exogenous HA inhibits the expression of α-smooth muscle protein and wound contraction. There exists dose-dependant effect.
Objective To explore the expression characteristics of chaperone interacting protein (CHIP) in normal, scar and chronic ulcer tissues and its relationship with wound healing. Methods Twenty biopsies including scar tissues(n=8), chronic ulcer tissues(n=4) and normal tissues(n=8)were used in this study. The immunohistochemical staining (power visionTMtwo-step histostaining reagent) was used to explore the amount and expression characteristics of such protein.Results The positive expression of CHIP was observed in fibroblasts, endothelial cells and epidermal cells in dermis and epidermis. It was not seen ininflammatory cells. The expression amount of CHIP in scar tissues, chronic ulcer tissues and normal tissues was 89%, 83% and 17% respectively. Conclusion Although the function of CHIP is not fully understood at present, the fact that this protein is expressed only at the mitogenic cells indicates that it may be involved in mitogenic regulation during wound healing.
Cell autophagy plays a key role in maintaining intracellular nutritional homeostasis during starvation through elimination of aberrant or obsolete cellular structures. The cellular cytoskeleton has a crucial role in multiple processes involving membrane rearrangements and vesicle-mediated events. Autophagy is mediated by both microtubules and actin networks: microtubules promote the synthesis of autophagosome and are related to the movement of autophagosome; actin networks have been implicated in structurally supporting the expanding of phagophore, moving autophagosomes and enabling their efficient fusion with the lysosome; non-muscle myosinⅡoperates in the early stages of autophagy during the initiation and expansion of the phagophore, whereas myosinⅥ and myosin 1C are involved in the late stages of autophagosome maturation and fusion with the lysosome, respectively. This review summarizes the multiple regulation of cytoskeleton on autophagy and focuses on the regulation of autophagy by actin and myosin, providing a new approach for the study of pathogenesis and innovative therapies of autophagy related diseases.
Hyperprolactinemia is the common clinical syndrome; the causes of hyperprolactinemia are physiological, pharmacological, and pathological, in which prolactinoma is the most common cause. In drug therapy, dopamine agonists are the first choice, but there are 10%–20% of the patients who are resistant to drug therapy. This paper mainly summarized the causes, treatments, mechanisms of drug resistance, treatment during pregnancy, and progresses in the treatment of prolactinoma, so as to provide some theoretical basis to further research of hyperprolactinemia.
Objective To observe the effects of cigarette smoke extract ( CSE) on the proliferation and secretion of hydrogen peroxide ( H2O2 ) in human lung fibroblasts ( HLFs) induced by transforming growth factor-β1 ( TGF-β1 ) . Methods Cultured HLFs were divided into a normal group and a model group induced by TGF-β1 ( 5 ng/mL) , then intervened with CSE at different concentrations ( 0% , 2. 5% , 5% ,10% , respectively) . Brdu ELISA assay was used to detect cell proliferation. H2O2 release from cultured cells was assayed using a fluorimetric method. Cellular localization of H2O2 and expression of α-SMA were performed using a fluorescent-labeling strategy. Results TGF-β1 stimulated group showed positive expression of α-SMA, implying TGF-β1 had induced fibroblasts to differentiate into myofibroblasts. In TGF-β1 stimulated group, 2. 5% and 5% CSE promoted cell proliferation ( P lt; 0. 01 or 0. 05) , while 10% CSE inhibited cell proliferation ( P lt; 0. 01) . In the normal group, both low and high concentration of CSE inhibited cell proliferation ( P lt; 0. 01 or P lt; 0. 05) , and the inhibition effect was dose-dependent. HLF induced by TGF-β1 generated low constitutive levels of extracellular H2O2 that was markedly enhanced by CSE treatment ( P lt; 0. 01) . Pretreatment with DPI, an inhibitor of NADPH oxidase, abolished secretion of H2O2 . Cellular localization of H2O2 by a fluorescent-labeling strategy demonstrated that extracellular secretion of H2O2 is specific to the myofibroblast. Conclusions Low concentration of CSE can promote myofibroblast proliferation, and markedly increase extracellular secretion of H2O2 . CSE possibly take part in the development and progress of idiopathic pulmonary fibrosis by increasing oxidative stress.
