Objective To investigate the development and significance of the expression of early growth response gene-1 （EGR-1） in autogenous vein graft in rats and detect the role of it in intimal hyperplasia. Methods Autogenous vein graft model was established in 90 Wistar rats, transplanting the right jugular vein to infra renal abdominal aorta by microsurgical technique. The vein graft samples were harvested at hour 1, 2, 6 and 24, day 3, 7,14, 28 and 42 after procedure. Normal vein as control group. Egr-1 mRNA was measured by reverse transcription-PCR and in situ hybridization. Western blot and immunohistochemistry were used to detect the protein expression of Egr-1. Results Intimal hyperplasia reached peak at day 28 after autogenous vein graft surgery. Egr-1 mRNA and Egr-1 protein hadn’t been found in the normal vein. The expressions of Egr-1 mRNA and Egr-1 protein had biphasic changes. By reverse transcription-PCR and in situ hybridization, we found that the level of Egr-1 mRNA rose at 1 hour after graft, the expression of Egr-1 mRNA was (35±7)%. Decline at hour 6， 24 and day 3, the positive rates of Egr-1 mRNA were (8±2)%, (8±6)% and (8±4)% respectively. Reincrease at day 7, a peak at day 28, the positive rate of Egr-1 mRNA was (45±6)% (compared with other phase, P＜0.01). At day 42, the expression of Egr-1 mRNA declined again. Immunohistochemical staining and Western blot revealed Egr-1 protein had expressed at hour 2 early phase, the expression of Egr-1 protein was (30±5)%, and until to hour 6. The level of Egr-1 protein was decrease at hour 24 and day 3, the positive rates were (7±3)% and (7±8)% respectively. A peak at day 28, the positive rate of Egr-1 protein was (40±9)% (compared with other phase, P＜0.01). We found that immu-noreative Egr-1 located vascular smooth muscle cells （VSMCs） and monocytes/macrophages in tunica media at the early phase of day 7 and 14, and in neointimal and medial VSMCs at later phase of day 28. Egr-1 was also present in the endoluminal endothelial cells. Conclusion In autogenous vein graft, Egr-1 plays an important role in the proliferation of VSMCs. Egr-1 may become a new target for the prevention and therapy of intimal hyperplasia, stenosis and emphraxis after vein graft.
ObjectiveTo summarize the therapeutic targets of pancreatic cancer (PC).
MethodsThe related literatures about the therapeutic targets of PC were reviewed.
ResultsPC was one of the most challenging tumor in worldwide, and was characterized as a highly aggressive disease with poor overall prognosis and a high mortality rate. The hallmark of PC was its poor response to radio-and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches which could significantly improve the clinical outcome of PC had been described, involving signal-transduction pathways, immune response, stroma reaction, and epigenetic changes.
ConclusionsMany therapeutic targets are involved in the treatment of PC. As current therapies failed to significantly improve the progression and the survival of PC, new therapeutic approaches and clinical studies are strongly required.
ObjectiveTo study the clinical value of procalcitonin (PCT), WBC count, and C-reactive protein (CRP) in diagnosis of common bile duct stones with acute bile duct infection and systemic inflammatory response syndrome (SIRS).MethodsA total of 80 patients with bile duct stones were retrospectively analyzed, which were divided into two groups, SIRS group (n=40) and non-SIRS group (n=40). The numerical value of PCT, WBC count, and CRP were detected on 1, 4, and 7 day after admission, and calculated the score of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) on 1 day after admission. Then analyzed the clinical value of PCT, WBC count, and CRP in diagnosis of common bile duct stones with acute bile duct infection and SIRS.ResultsEach area under the ROC curve of PCT, CRP, and WBC count were 0.81, 0.78, and 0.72, respectively, with significant difference (P<0.05). The PCT, CRP, and WBC count had a certain accuracy in diagnosis of common bile duct stones with acute bile duct infection and SIRS. The positive-relationship between PCT, CRP, WBC count and APACHE Ⅱ score was significant (r=0.91, P<0.01; r=0.88, P<0.01; r=0.69, P<0.01).ConclusionTo detect the numerical value of PCT, WBC count, and CRP had significant clinical value in diagnosis of common bile duct stones with acute bile duct infection and SIRS.
The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy combined with surgery, but patients after the same treatment regimen show a large difference in outcomes. For patients with good response to neoadjuvant therapy, the waiting & observation scheme can be selected to avoid surgery and other complications. Therefore, accurate assessment of the response of patients with locally advanced rectal cancer after neoadjuvant therapy can better develop personalized treatment strategies. Current studies have found that blood sample detection, endoscopy, imaging examination and artificial intelligence have their own advantages and disadvantages in evaluating the response of neoadjuvant therapy. Therefore, this article reviews the application of different clinical tools in evaluating and predicting the response of neoadjuvant therapy for locally advanced rectal cancer, and looks forward to the future development direction.
Objective To investigate the regulatory effects of miR-26a-5p on the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) by regulating cAMP response element binding protein 1 (CREB1). Methods The adipose tissues of four 3-4 weeks old female C57BL/6 mice were collected and the cells were isolated and cultured by digestion separation method. After morphological observation and identification by flow cytometry, the 3rd-generation cells were subjected to osteogenic differentiation induction. At 0, 3, 7, and 14 days after osteogenic differentiation induction, the calcium deposition was observed by alizarin red staining, ALP activity was detected, miR- 26a-5p and CREB1 mRNA expressions were examined by real-time fluorescence quantitative PCR, and CREB1 protein and its phosphorylation (phospho-CREB1, p-CREB1) level were measured by Western blot. After the binding sites between miR-26a-5p and CREB1 was predicted by the starBase database, HEK-293T cells were used to conduct a dual-luciferase reporter gene experiment to verify the targeting relationship (represented as luciferase activity after 48 hours of culture). Finally, miR-26a-p inhibitor (experimental group) and the corresponding negative control (control group) were transfected into ADSCs. Alizarin red staining, ALP activity, real-time fluorescent quantitative PCR (miR-26a-5p) and Western blot [CREB1, p-CREB1, Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN)] were performed at 7 and 14 days after osteogenic induction culture. Results The cultured cells were identified as ADSCs. With the prolongation of osteogenic induction culture, the number of calcified nodules and ALP activity significantly increased (P<0.05). The relative expression of miR-26a-5p in the cells gradually decreased, while the relative expressions of CREB1 mRNA and protein, as well as the relative expression of p-CREB1 protein were increased. The differences were significant between 7, 14 days and 0 day (P<0.05). There was no significant difference in p-CREB1/CREB1 between different time points (P>0.05). The starBase database predicted that miR-26a-5p and CREB1 had targeted binding sequences, and the dual-luciferase reporter gene experiment revealed that overexpression of miR-26a-5p significantly suppressed CREB1 wild-type luciferase activity (P<0.05). After 7 and 14 days of osteogenic induction, compared with the control group, the number of calcified nodules, ALP activity, and relative expressions of CREB1, p-CREB1, OCN, and RUNX2 proteins in the experimental group significantly increased (P<0.05). There was no significant difference in p-CREB1/CREB1 between the two groups (P>0.05). Conclusion Knocking down miR-26a-5p promoted the osteogenic differentiation of ADSCs by up-regulating CREB1 and its phosphorylation.
ObjectiveTo systematically review the response of Kawasaki disease (KD) after an initial standard dose of intravenous immunoglobulin (IVIG) therapy and routine laboratory indexes.MethodsWe searched PubMed, EMbase, The Cochrane Library, CBM, CNKI, VIP and WanFang Data databases to collect case-control studies about the correlation between response of KD after an initial standard dose of IVIG therapy and routine laboratory indexes till 31st December 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. A meta-analysis was performed by using RevMan 5.3 software.ResultsThirty studies were included. The results of meta-analysis demonstrated that the levels of hemoglobin (Hb) (SMD=–0.21, 95%CI –0.32 to –0.09, P<0.001), serum albumin (ALB) (SMD=–0.68, 95%CI –0.90 to –0.47,P<0.001) and serum sodium (SMD=–0.64, 95%CI –1.01 to –0.27,P<0.001) in IVIG non-responsiveness group were significantly lower than those in IVIG responsiveness group. The levels of alanine aminotransferase (ALT) (SMD=0.74, 95%CI 0.36 to 1.13,P<0.001), aspartate aminotransferase (AST) (SMD=0.61, 95%CI 0.24 to 0.99,P=0.001) and C-reactive protein (CRP) (SMD=0.63, 95%CI 0.38 to 0.87, P<0.001) in IVIG non-responsiveness group were higher than those in the IVIG responsiveness group.ConclusionThe current evidence shows that low levels of Hb, ALB and serum sodium and high levels of CRP, ALT, and AST are risk factors of IVIG non- responsiveness in KD. Due to limited quality and quantity of included studies, more high-quality studies are needed to verify the conclusion.
Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer. Nowadays, gemcitabine and cisplatin in combination have been adopted as the first-line chemotherapy for patients with NSCLC. This study aimed to monitor early response to combined chemotherapy of gemcitabine plus cisplatin in a mouse model of NSCLC by using 18F-fluorodeoxyglucose and 18F-fluorothymidine small animal positron emission tomography (PET). Lewis lung carcinoma-bearing C57BL/6 mice were treated with gemcitabine-cisplatin or saline. Small animal PET with 18F-FDG and 18F-FLT was performed before (baseline) and after treatment (on Day 3), respectively. Imaging results were confirmed by histopathological studies (hematoxylin and eosin staining, Ki67 staining). Compared to the results in the control group, gemcitabine-cisplatin in the treated group significantly inhibited tumor growth (P<0.05). In the treated group, the maximum standardized uptake value (SUVmax) of 18F-FLT decreased significantly from 0.59±0.05 (baseline) to 0.28±0.05 (Day 3) (P<0.05). There was no significant difference between baseline (4.35±0.46) and that on Day 3 (4.02±0.47) on 18F-FDG SUVmax (P>0.05). The proliferation of tumor assessed by Ki67 staining decreased significantly after treatment of one dose of gemicitabine-cisplatin (P<0.05). The staining of HE showed an increase in necrotic and inflam- matory cells after the treatment. This study demonstrated that the uptake of 18F-FLT reduced more rapidly and signi-ficantly than that of 18F-FDG and was less disturbed by the increase of inflammatory cells after chemotherapy.
Objective To study the method of obtaining a large number of dendritic cells （DC）. To study the specific cytotoxicity T lymphocyte (CTL) effect against tumor cells initiated by DC pulsed with peptide of cancer cell. Methods Development of cells with cytologic features of DC in bone marrow cultures supplemented with granulocyte macrophage-colony stimulus factor (GM-CSF) and IL-4. Determining the DC phenotype and the specific structure by electronic microscopy. The CTL effect against pancreatic carcinoma leading by the DC pulsed with tumor cells lysate in vitro was observed. Results A large number of typical DC was proliferated by supplementing with GM-CSF and IL-4 cytokines. DC had specific cell appearance and structure, and highly expressed various cell surface molecules. TNF-α had the ability of stimulating DC mature, the mature DC had the enhancing abilities of antigen presenting and IL-12 self-secreting, as well as, expressed higher levels of CD54， MHC-Ⅱ and CD86 molecules than control group (P＜0.05). T lymphoid cell stimulated by DC without tumor antigen could not recognize and kill the target cells, only if DC pulsed with peptide of cancer cell can lead a b immune response to special tumor cells. The inhibiting ratio of CTL was significantly higher than that in other groups (P＜0.01). Conclusion Bone marrow DC has b ability of inducing special CTL against determined cancer cells after they are pulsed with tumor cell lysate. DC vaccine is probably a new immunotherapeutic method against tumor in the near future.
Objective To investigate the effective dose of remimazolam benzenesulfonate to suppress cardiovascular responses to laryngeal mask placement in elderly patients. Methods Elderly patients undergoing laryngeal mask anesthesia between March and June 2023 were selected. Combined with sulfentanil 0.2 μg/kg, remimazolam was used as induction hypnotic. The first patient was given remizolam benzenesulfonate 0.16 mg/kg infused by pump for 1 min. The dose of remimazolam for the next patient was determined by the biased coin up-and-down method based on the patient’s response to the laryngeal mask placement. The score of Modified Observer’s Assessment of Alert/Sedation, vital signs and anesthesia depth index (AI) were recorded during induction. Probit analysis was used to calculate the half effective dose (ED50), 95% effective dose (ED95) and half effective AI (AI50). According to the statistical requirements, at least 45 negative patients were required. Results A total of 53 elderly patients were enrolled in the study until the end of the trial. The ED50 and ED95 of remimazolam benzenesulfonate for inhibiting cardiovascular responses to laryngeal mask insertion were 0.154 mg/kg [95% confidence interval (CI) (0.034, 0.170) mg/kg] and 0.207 mg/kg [95%CI (0.190, 0.614) mg/kg], respectively. AI decreased during induction, with an AI50 of 64.119 [95%CI (60.609, 69.984)]. Conclusion When combined with 0.2 μg/kg sufentanil, infusing 0.2 mg/kg remimazolam benzenesulfonate for 1 min is effective and safe for laryngeal mask anesthesia induction in elderly patients.
ObjectiveTo systematically evaluate the dose-response relationship between coffee consumption and liver cancer risk. MethodsThe PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, WanFang Data, and CBM databases were searched from inception to December 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 17.0 software. ResultsFifteen studies (11 cohort studies and 4 case-control studies) involving 557 259 participants were included. The results of meta-analysis showed that coffee consumption was significantly negatively associated with the risk of liver cancer (RR=0.39, 95%CI 0.27 to 0.57, P<0.01). The dose-response meta-analysis showed a non-linear dose-response relationship between coffee consumption and the risk of liver cancer (P<0.01). Compared with people who did not drink coffee, people who drank 1 cup of coffee a day had a 25% lower risk of liver cancer (RR=0.75, 95%CI 0.67 to 0.83), and people who drank 2 cups of coffee a day had a 38% lower risk of liver cancer (RR=0.62, 95%CI 0.56 to 0.70). The risk of liver cancer decreased by 45% (RR=0.55, 95%CI 0.48 to 0.62) for 3 cups of coffee and by 51% (RR=0.49, 95%CI 0.43 to 0.56) for 4 cups of coffee. ConclusionCurrent evidence suggests that there is a nonlinear dose-response relationship between coffee consumption and the risk of liver cancer. These results indicate that habitual coffee consumption is a protective factor for liver cancer. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
