ObjectiveTo investigate the expression of tumor suppressor gene Tat interacting protein 30 (TIP30) gene in papillary thyroid carcinoma and it’s clinical significance in treatment of thyroid carcinoma. Methods Thirty cases of pathological specimens wax pieces of papillary thyroid carcinoma from 2003 to 2006 in our hospital were selected, in which there were 7 male, 23 female； and the age was from 15 to 70 years old, average 44.7 years. Six cases were nodular goiter with carcinomatous change in local area (papillary), 2 cases were thyroid capsular invasion. Distant lymph node metastasis and lesions surrounding the thyroid tissue were not confirmed by pathology. Every specimen was divided into tumor tissue and adjacent tissue (1-2 cm far away from tumor and non-cancerous tissue was confirmed by pathology). The expression of TIP30 in specimen was detected by immunohistochemical method with staining index and the average absorbance. ResultsTIP30 was expressed in the cell membrane and cytoplasm, which was showed as brown particles. ①Staining index: TIP30 in adjacent tissues was expressed highly with 21 (70.0%) positive cases (gt;2 points) and 9 (30.0%) negative cases (≤2 points), while its expression in cancer tissues was reduced or missed with 11 (36.7%) positive cases (gt;2 points) and 19 (63.3%) negative cases (≤2 points). There was a statistical difference between them (P＜0.05), and it was not related to age and gender of patients (Pgt;0.05). ②The average absorbance of TIP30 in cancer tissues was significantly lower than that in adjacent tissue (P＜0.05). ConclusionThe expression of TIP30 in papillary thyroid carcinoma is reduced or deleted, which can supply some theory support for its gene therapy.
ObjectivesTo systematically review the methods of pharmacoeconomic evaluation model for hepatitis C therapies and to identify shortcomings of the existing modeling research by comparing the model structure, hypothesis and methodological differences, and to provide suggestions for the construction of high-quality hepatitis C pharmacoeconomic evaluation models.MethodsPubMed, EMbase, The Cochrane Library, CNKI and WanFang Data databases were electronically searched to collect relevant literatures on the pharmacoeconomic evaluation models for hepatitis C therapies from August 2014 to August 2019. Two reviewers independently screened literature, extracted data, and evaluated the quality of the included studies. Then, the data related to the model structure, methods, and assumptions were compared and summarized.ResultsMost of the 46 studies that finally included used similar modeling methods. Ignoring different modeling elements would cause overestimation or underestimation of the value of hepatitis C therapies. Model structure of all studies were similar and key parameters were from the same source. Forty-five studies measured the cost of drugs and medical cost of health status. All studies used quality-adjusted life years as the outcome and reported incremental cost-effectiveness ratio. Thirty studies conducted one-way sensitivity analysis and probability sensitivity analysis.ConclusionsThe included studies share similar methodological designs and have high quality in general. However, there are some differences and deficiencies in research perspective, model types, model assumptions and model verification. Future pharmacoeconomic evaluation model of hepatitis C therapies should report the results of the whole society, establish dynamic model to consider the impact of transmission, make half-cycle correction for long periods, consider the recurrence after cure, model liver transplantation, and verify the model.
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 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.
ObjectiveTo compare the effectiveness of sequestrum clearance and impacting bone graft via surgical hip dislocation approach and core decompression and bone graft for avascular necrosis of the femoral head (ANFH) at Association Research Circulation Osseous (ARCO) stage Ⅲ.MethodsA clinical data of 60 patients (69 hips) of non-traumatic ANFH at ARCO stage Ⅲ, which met the inclusion criteria between October 2013 and April 2016, was retrospectively analyzed. Among them, 24 patients (28 hips) were treated with sequestrum clearance and impacting bone graft via surgical hip dislocation approach (group A); and 36 patients (41 hips) were treated with core decompression, sequestrum clearance, impacting bone graft, and nonvascular fibular allograft supporting (group B). There was no significant difference in gender, age, disease duration, affected side, type and stage of the ANFH, and preoperative Harris hip score and visual analogue scale (VAS) score between the two groups (P>0.05). After operation, the function of the hip was evaluated by Harris hip score, imaging examination was performed to observe the femoral head shape and evaluate whether the hip preserving success.ResultsThe incisions of two groups healed by first intention. All patients were followed up. The follow-up time was 12-48 month (mean, 25.8 months) in group A and 12-54 months (mean, 26.4 months) in group B. At last follow-up, 5 hips in group A were classified as clinical failure, femoral head survival rate was 82.1%, the median survival time was 43 months. While 19 hips in group B were classified as clinical failure, femoral head survival rate was 53.7%, the median survival time was 42 months. There was significant difference in survival curve distribution between the two groups (χ2= 4.123, P=0.042), and the surgical procedures of group A was superior to group B. In the two groups, the Harris hip scores at last follow-up were significantly higher than preoperative ones (P<0.05), and VAS scores were significantly lower than preoperative ones (P<0.05). There was no significant difference in Harris hip score and VAS score at last follow-up between the two groups (P>0.05). All grafted bones got fusion according to the X-ray films, and there was no significant difference in the fusion time between the two groups (t=0.752, P=0.456). In group A, greater trochanter bone cutting were healed well; and the heterotopic ossification around the hip joint occurred in 1 case.ConclusionThe surgery of impacting bone graft via surgical hip dislocation approach and core decompression and bone graft can be applied to treat ANFH at ARCO stage ⅢA which was mild collapse and satisfactory effectiveness can be obtained. While for the patients of ANFH at ARCO stage Ⅲ B with severe collapse, the hip survival rate of the former is better than that of the latter.
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 investigate the effect of picroside Ⅱ (PIC Ⅱ) on the pyroptosis and thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway in alveolar epithelial cells of severe pneumonia rats. Methods A severe pneumonia rat model was constructed and all experimental rats were divided into a control group, a severe pneumonia group, low, medium, and high dose PIC Ⅱ groups (PIC Ⅱ-L, PIC Ⅱ-M, PIC Ⅱ-H groups), and a high-dose PIC Ⅱ+TXNIP/NLRP3 pathway activator trimethylamine oxide group (PIC Ⅱ-H+TMAO group). The levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were detected by ELISA; Wright’s staining was applied to detect eosinophil count (EOS), lymphocyte count (LYM), and neutrophil count (NEU) in the sediment of alveolar lavage fluid. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. The expressions of cysteine aspartate protease 1 (Caspase-1) and dermatin D (GSDMD) were detected by immunohistochemistry. The expressions of TXNIP, NLRP3 and apoptosis-associated microprotein (ASC) were detected by Western blot. Results Compared with the control group, the severe pneumonia group had severe lung tissue injury, obvious inflammatory cell infiltration, and increased expressions of TNF-α, IL-1β, IL-6, EOS, LYM, NEU, Caspase-1, GSDMD, TXNIP, NLRP3 and ASC (all P<0.05). Compared with the severe pneumonia group, lung tissue injury in PIC Ⅱ-L, PIC Ⅱ-M and PIC Ⅱ-H groups was reduced successively, and inflammatory cell infiltration was gradually reduced. The expressions of TNF-α, IL-1β, IL-6, EOS, LYM, NEU, Caspase-1, GSDMD, TXNIP, NLRP3 and ASC were decreased successively (all P<0.05). Compared with the PIC Ⅱ-H group, the PIC Ⅱ-H+TMAO group showed increased lung tissue damage and obviously increased inflammatory cell infiltration, the expression of TNF-α, IL-1β, IL-6, EOS, LYM, NEU, Caspase-1, GSDMD, TXNIP, NLRP3, and ASC were obviously increased (all P<0.05). Conclusion PIC Ⅱ inhibits pyroptosis of alveolar epithelial cells in severe pneumonia rats by inhibiting the TXNIP/NLRP3 pathway.
Objective To study the function and mechanism of G protein coupled receptor kinase interacting protein 1(GIT1) RNA hairpin (GIT1-RNAh) in osteoblast migration. Methods The sixth passage osteoblasts were divided into 2 groups and were infected by GIT1-RNAh (experimental group) and green fluoresence protein RNA hairpin (GFP-RNAh) (control group) adenovirus for 12 hours respectively. Each group was further classfied into two groups according to with or without platelet-drived growth factor (PDGF) stimulation. The GIT1 expression and Paxillindistribution was analyzed by immunofluorescence staining. Paxillin phosphorylation was detected by Western Blot. The localization of Paxillin was determined by co-immunofluorescence staining after transfection with cyanine fluorescence protein tagged GIT1RNAh (CFP-GIT1-RNAh)(experimental group) and GFP-RNAh (CFP-GFP-RNAh)(control group). The role of GIT1-RNAh (experimental group) and GFP-RNAh (control group) adenovirus in osteoblasts migration was determined by wound healing assay. Results Immunofluorescence staining results showed that the GIT1-RNAh significantly inhibited endogenous GIT1 expression, interfered Paxillin distribution.Western Blot results showed that Paxillin phosporylation was obviously inhibited in osteoblasts infected with GIT1-RNAh adenovirus (P＜0.05). The wound healing assay results howed that GIT1-RNAh adenovirus significantly inhibited osteoblast migration induced by PDGF. Conclusion GIT1-RNAh inhibits osteoblasts migration by interfering paxillin distribution and decrease Paxillin phosphorylation.
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.
Vascular smooth muscle cells (VSMCs) phenotype switching plays an essential role in the pathogenesis of various vascular diseases. The present study aims to investigate the role of receptor-interacting protein kinases 1(RIPK1) in VSMCs phenotypic switching induced by Angiotensin Ⅱ(Ang Ⅱ). Expression of mRNA and protein of RIPK1, markers of VSMCs phenotypic switching and secretion, phosphorylation of the P65 subunit of NF-κB were measured by real-time PCR and Western blot. Meanwhile, EdU incorporation assay and wound scratch assay were performed to determine the cell proliferation and migration respectively. At the same time, Necrostatin-1(Nec-1, an known RIPK1 inhibitor) and RIPK1-specific small interference RNA (siRNA) were used to inhibit the expression of RIPK1. The experimental data demonstrated that the mRNA and protein levels of RIPK1 and P65 phosphorylation were increased significantly in the process of VSMC phenotypic switching induced by Ang II. Moreover, the expression of RIPK1 and P65 phosphorylation were significantly down-regulated in VSMCs pretreated with Nec-1 or trans-fected with RIPK1-siRNA. Furthermore, the proliferation, secretion and migration of VSMCs were also markedly suppressed after inhibition of RIPK1 by Nec-1 or its specific siRNA. The results suggested that RIPK1 might be involved in VSMC phenotypic switching induced by Ang II, which was possibly via up-regulating the NF-κB signaling pathway.