[Research on the mechanism of shengxian and jinshuiliujun decoction in treating silicosis based on network pharmacology].

Objective: To explore the active ingredients of shengxian and jinshuiliujun decoction with the method of network pharmacology, and to verify the experimental mechanism of its treatment of silicosis. Methods: In May 2023, the active ingredients and targets of drugs in shengxian and jinshuiliujun decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The target of silicosis disease was screened by databases such as Genecards, Disease Gene Network (DisGeNET), Comparative Toxicogenomics Database (CTD), etc. The screened drug targets and disease targets were intersected to obtain the target set of shengxian and jinshuiliujun decoction for the treatment of silicosis. Protein-protein interaction (PPI) network analysis was performed on the target set through STRING database, and core target genes were screened. GO enrichment analysis and KEGG pathway analysis of intersection genes were performed based on Metascape database, and molecular docking verification of key components and targets of shengxian and jinshuiliujun decoction was carried out. Twenty-four adult male SD rats with SPF grade were randomly divided into control group, model group and TCM intervention group, with 8 rats in each group. The dust-stained rat model was prepared by non-tracheal exposure of 1 ml silica suspension (50 mg/ml) in one go, and TCM intervention group was given shengxian and jinshuiliujun decoction[6 g/ (kg·d) ] on the second day. The CT of the lungs of each group was observed 28 days after the dust-stained rat model. Paraffin sections of rat lung tissues were prepared and stained with Hematoxylin-Eosin (HE) and Masson. Western blot was used to verify the expression of core target-related proteins in rat lung tissues after the intervention of shengxian and jinshuiliujun decoction for 28 days, and the differences in protein expression between groups were compared by one-way analysis of variance. Results: A total of 205 active ingredients and 3345 active compounds were selected from shengxian and jinshuiliujun decoction, corresponding to 281 targets, among which 240 targets were related to silicosis. Serine/threonine kinase 1 (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF) and interleukin (IL) 6 may be the key targets of shengxian and jinshuiliujun decoction in the treatment of silicosis. Through enrichment analysis, 30 GO entries and 20 potential signaling pathways were screened according to P-value, including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) and cancer signaling pathways. Molecular docking showed that the active compounds of shengxian and jinshuiliujun decoction had good binding with the core target proteins, and the strongest binding properties were beta-sitosterol and TNF-α (-10.45 kcal/mol). In animal experiments, the inflammatory infiltration and fibrosis of lung tissue of rats in TCM intervention group were significantly improved. Compared with control group, the levels of TNF-α, IL-1ß, IL-6 and NF-κB in lung tissue of model group were significantly increased (P<0.05). Compared with model group, the lung injury of rats in TCM intervention group was significantly improved, and the expressions of TNF-α, IL-1ß, IL-6 and NF-κB were significantly decreased (P<0.05) . Conclusion: Shengxian and jinshuiliujun decoction in the treatment of silicosis may play an anti-fibrosis role by inhibiting the NF-κB signal transduction pathway mediated by inflammatory factors such as TNF-α and IL-1ß, which provides a reference for further exploring the material basis and mechanism of its action.

[Effects of M2-type macrophages and GKT137831 on oxidative stress in hepatic stellate cells].

Objective: To investigate the effects of reduced nicotinamide adenine dinucleotide phosphooxidase 4 (NOX4) inhibitors GKT137831 and M2-type macrophages on oxidative stress markers NOX4, nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the rat hepatic stellate cell line (HSC-T6). Methods: Rat bone marrow macrophages were extracted and induced using interleukin (IL)-4 to differentiate them into M2 phenotype macrophages. HSC-T6 activation was performed with 5 µg/L transforming growth factor ß1 (TGF-ß1). The proliferation condition of HSC-T6 cells stimulated by the NOX4 inhibitor GKT137831 at a concentration gradient of 5 to 80 µmol/L after 48 hours was detected using the Cell Counting Kit-8 (CCK-8) assay. The optimal drug concentration was chosen and divided into an HSC co-culture group (the control group) and five experimental groups: the TGF-ß1 stimulation group, the TGF-ß1 +GKT137831 stimulation group, the M2-type macrophage + HSC co-culture group, the M2-type macrophage +TGF-ß1 stimulation group, and the M2-type + TGF-ß1 + GKT137831 stimulation group. Reactive oxygen species (ROS) production level was detected in each cell using the DCFH-DA probe method. NOX4, α-smooth muscle actin (α-SMA), Nrf2, and HO-1 levels in each group of HSC cells were detected using the qRT-PCR method and the Western blot method. The t-test was used to compare the two groups. The one-way ANOVA method was used to compare multiple groups. Results: Intracellular ROS increased significantly following TGF-ß1 stimulation. ROS relative levels in each cell group were 1.03±0.11, 3.88±0.07, 2.90±0.08, 0.99±0.06, 3.30±0.05, 2.21±0.11, F = 686.1, P = 0.001, respectively. The mRNA and protein expressions of NOX4, α-SMA, Nrf2, and HO-1 were significantly increased (P < 0.05). After the addition of GKT137831, ROS, and NOX4, α-SMA mRNA and protein expression were comparatively decreased in the TGF-ß1 stimulation group (P < 0.05), while mRNA and protein expressions of Nrf2 and HO-1 were increased (P < 0.05). The expression of ROS and NOX4, as well as α-SMA mRNA and protein, produced by HSC were significantly decreased in the co-culture group compared to the single culture group after TGF-ß1 stimulation (P < 0.05). After the addition of GKT137831, ROS, NOX4, α-SMA mRNA, and protein expression were further reduced in the co-culture group compared with the single culture group (P < 0.05), while the mRNA and protein expression of Nrf2 and HO-1 were further increased (P < 0.05). Conclusion: NOX4 inhibitor GKT137831 can reduce RO, NOX4, and α-SMA levels while increasing Nrf2 and HO-1 levels in hepatic stellate cells. After M2-type macrophage co-culture, GKT137831 assists in lowering ROS, NOX4, and α-SMA levels while accelerating Nrf2 and HO-1 levels in hepatic stellate cells, which regulates the balance between oxidative stress and anti-oxidative stress systems, thereby antagonizing the fibrosis process.

[The impact of extended waiting time on tumor regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer].

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

[The anatomic zone localization based on biparametric MRI for the prediction of the risk degree of prostate cancer].

Objective: To investigate the anatomic zone localization based on biparametric magnetic resonance imaging (bpMRI) for the prediction of the risk degree in patients with prostate cancer. Methods: A total of 92 patients with prostate cancer confirmed by radical surgery in First Affiliated Hospital, Air Force Medical University, from January 2017 to December 2021 were collected. All patients underwent bpMRI (non-enhanced scan and DWI). According to ISUP grade, those patients were divided into low-risk group [≤grade 2, n=26, aged 71 (64.0, 5.2) years] and high-risk group[≥grade 3, n=66, aged 70.5 (63.0, 74.0) years]. The interobserver consistency test for ADC values was evaluated using the intraclass correlation coefficients (ICC). The differences in total prostate specific antigen (tPSA) between the two groups were compared and the χ2 test was used to compare the differences in the risk of prostate cancer in the transitional and peripheral zone. Independent correlation factors for prostate cancer risk were analyzed by logistic regression using high and low risk of prostate cancer as dependent variables, including factors such as anatomical zone, tPSA, apparent diffusion coefficient mean (ADCmean), apparent diffusion coefficient minimum (ADCmin) and age. Receiver operating characteristic (ROC) curves were plotted to assess the efficacy of the combined models of anatomical zone, tPSA, and anatomical partitioning+tPSA for diagnosing prostate cancer risk. Results: The ICC values of the ADCmean and ADCmin between the observers were 0.906 and 0.885, respectively, with good agreement. The tPSA in the low-risk group was lower than that in the high-risk group [19.64 (10.29, 35.18) ng/ml vs 72.42 (24.79, 187.98) ng/ml; P<0.001]; the risk of prostate cancer in the peripheral zone was higher than that in the transitional zone, and the difference was statistically significant (P<0.01). Multifactorial regression showed that anatomical zones (OR=0.120, 95%CI:0.029-0.501, P=0.004) and tPSA (OR=1.059, 95%CI:1.022-1.099, P=0.002) were risk factors for prostate cancer risk. The diagnostic efficacy of the combined model (AUC=0.895, 95%CI: 0.831-0.958) was better than the predictive efficacy of the single model for both anatomical partitioning (AUC=0.717, 95%CI:0.597-0.837) and tPSA (AUC=0.801, 95%CI: 0.714-0.887) (Z=3.91, 2.47; all P<0.05). Conclusions: The malignant degree of prostate cancer in peripheral zone was higher than that in transitional zone. Combination of anatomic zone located by bpMRI and tPSA can be used to predict the risk of prostate cancer before surgery, expected to provide support for patients to develop personalized treatment strategies.

B cells and tertiary lymphoid structures are associated with survival in papillary thyroid cancer.

PURPOSE: The function of B cells in papillary thyroid cancer (PTC) is controversial. The role of B-cell-related tertiary lymphoid structures (TLSs) is still unclear. Whether B cells exert their anti-tumor effect through forming TLS in PTC needs further investigation. METHODS: We detected the percentage of B cells in PTC tissues by multi-parameter flow cytometry. Paraffin-embedded tumor tissues of 125 PTC patients were collected and stained with Haematoxylin-Eosin (H&E) for inflammatory infiltration analysis in combination with clinical features. Multiplexed immunohistochemistry (mIHC) was performed to verify the TLSs in above inflammatory infiltration. Correlation of B cells and TLSs with prognosis was analyzed using the TCGA database. RESULTS: We observed that PTC patients with higher expression of B lineage cell genes had improved survival and the percentage of B cells in the PTC tumor tissues was variable. Moreover, PTC tumor tissues with more B cells were surrounded by immune cell aggregates of varying sizes. We furtherly confirmed the immune cell aggregates as TLSs with different maturation stages. By analyzing PTC data from TCGA database, we found the maturation stages of TLSs were associated with genders and clinical stages among PTC patients. Moreover, patients with high TLSs survived longer and had a better prognosis. CONCLUSION: B cells are associated with the existence of TLSs which have different maturation stages in PTC. Both B cells and TLSs are associated with the survival rate of PTC. These observations indicate that the anti-tumor effects of B cells in PTC are associated with TLSs formation.

[Analysis on the rationality of input and output of occupational health funds in an iron and steel enterprise].

Objective: To analyzes the various occupational health investment and occupational health output of a steel enterprise, and propose a reasonable occupational health investment plan for this enterprise. Methods: In march 2016, various occupational health input and output data of various branches of an iron and steel company in 2015 were collected, and the efficiency of occupational health inputs and outputs of each branch was evaluated using data envelopment analysis (DEA) , and the branches with non-optimal efficiency were adjusted to propose a reasonable occupational health investment plan. Results: Among the branch plants investigated by this steel company, the occupational health input-output efficiency values of ironmaking north plant, power plant, hot rolling plant and stainless steel plant were 1, while the occupational health input-output efficiency of gas making plant, cold rolling plant, metallurgical furnace charge plant, coking plant, ironmaking south plant and long product plant were not the best, and the cold rolling plant has the lowest efficiency value of 0.759. For the cold rolling plant, only the parameters of acid rolling plant satisfy α=1 and s(-)=0, s(+)=0, while the remaining four workshops do not meet. After adjusting the inputs of each part according to the parameters, the occupational health output of the remaining four workshops can reach 1.7044, 2.0238, 1.3152 and 1.2136 times of the current workshop, respectively. Adjustment plans for other branch factories with unreasonable investment structures are also presented in the corresponding tables. Conclusion: The occupational health investment structure of the ironmaking south plant and other branches in this steel enterprise is unreasonable, and the adjustment using data envelopment analysis can maximize the benefits of its occupational health output.

The significance of Hashimoto's thyroiditis for postoperative complications of thyroid surgery: a systematic review and meta-analysis.

INTRODUCTION: Hashimoto's thyroiditis (HT) is one of the most common immune-mediated diseases. It makes thyroid surgery more complicated and difficult because there may be adhesions between the thyroid gland and surrounding structures. However, it is still controversial whether HT patients carry a high risk for postoperative complications of thyroid surgery. The purpose of this study was to investigate the significance of HT for the postoperative complications of thyroid surgery. METHODS: A search for studies assessing the postoperative complication risks of HT patients compared with that of patients with benign nodules (BNs) was performed in PubMed, EMBASE and Web of Science. Nine studies (20,118 cases, 1,582 cases of HT and 18,536 cases of BN) were identified, and the data from the relevant outcomes were extracted and analysed. RESULTS: There were no significant differences between the HT group and BN group in recurrent laryngeal nerve palsy (RLNP) and permanent hypoparathyroidism (PHP). The rate of transient hypocalcaemia (THC) was significantly higher in the HT group (16.85%) than in the BN group (13.20%). CONCLUSIONS: The meta-analysis showed that HT only increased the risk of the postoperative complication THC compared to BN. Understanding the significance of HT in postoperative hypoparathyroidism after thyroid surgery would help clinicians perform sufficient preoperative (and postoperative) assessments and to optimise surgical planning.

[Analysis of occupational health input-output of a iron mine in Hebei province].

Objective: To explore the relationship between input and output of occupational health funds, and to provide basis for relevant departments to make decisions. Methods: In September 2018, a state-owned iron ore in Hebei Province (mining history of more than 10 years, which can represent the general type of iron ore) was selected as the research object. Through the investigation and collection of enterprise general situation, occupational health input, loss and output related indicators, the iron mine occupational health expenditure input-output table and model were established, and the digital relationship between the investment and output was solved by MATLAB software. Results: The labor consumption in the departments of underground mining, open pit mining, crushing and rock discharging, transportation, tailings and mineral processing (taking labor wages as reference) were 756.46, 1.281.78, 987.61, 1 570.71, 50.956 and 18.9116 million yuan/year respectively. The output value of each sector is 11 207.19, 18 989.95, 15 176.40, 25 294.00, 7.704.94 and 280.1797 million yuan/year respectively. The ratio of health input to total output was 0.004 5, and the ratio of occupational health input to output was 1/0.046. Conclusion: The input-output table model of occupational health in iron mine can reflect the relationship between input and output of occupational health funds. The input situation of the coal mine is poor, and the input does not bring obvious occupational health benefits.

Development and validation of a three-immune-related gene signature prognostic risk model in papillary thyroid carcinoma.

PURPOSE: Increasing evidence indicates that there is a correlation between papillary thyroid carcinoma (PTC) prognosis and the immune signature. Our goal was to construct a new prognostic tool based on immune genes to achieve more accurate prognosis predictions and earlier diagnoses of PTC. METHODS: The 493 PTCs samples and 58 tumor-adjacent normal tissues were obtained from The Cancer Genome Atlas database (TCGA). Immune genes were obtained from the ImmPort database. First, this cohort was randomly divided into training cohort and testing cohort. Second, the differentially expressed (DE) immune genes from the training set were used to construct the prognostic model. Then, the testing and entire data cohorts were used to validate the model, and the data were analyzed to determine the correlation of the clinical prognostic model with immune cell infiltration and expression profiles of human leukocyte antigen (HLA) genes. Finally, an analysis of the gene ontology (GO) annotation was performed. RESULTS: A total of 189 upregulated and 128 downregulated DE immune genes were identified. We developed and validated a three-immune gene model for PTC that includes Hsp70, NOX5, and FGF23. This model was demonstrated to be an independent prognostic variable. In addition, the overall immune activity of the high-risk group was higher than that of the low-risk group. CONCLUSIONS: We developed and validated a three-immune gene model for PTC that includes HSPA1A, NOX5, and FGF23. This model can be used as a validated tool to predict outcomes in PTC.

von Willebrand factor promotes platelet-induced metastasis of osteosarcoma through activation of the VWF-GPIb axis.

von Willebrand factor (VWF) is exclusively expressed in endothelial cells (ECs) and megakaryocytes, which plays a crucial role in the initiation of arterial thrombosis. Recent studies have shown that VWF is also expressed in osteosarcoma (OS) cells and participates in adhesion of cancer cells to platelets, thus promoting metastasis of OS cells. However, it is unclear how OS cell-derived VWF-platelet interaction contributes to the metastasis of OS. We hypothesized that the interaction is mediated by the binding between VWF A1 and GPIbα of platelets, a molecular mechanism similar to that of thrombosis. The increased expression of VWF in SAOS2 cells may contribute to the enhancement of platelet adhesion through the VWF-GPIb pathway, which could promote the migration and invasion capacities of SAOS2 cells in vitro. Antibodies that block the pathway could significantly inhibit the platelet-induced metastasis of OS cells. Our results suggest a theoretical basis for the development of new anti-OS metastasis drugs, and further enrich the mechanism of OS metastasis.

Long noncoding RNA DLX6-AS1 functions as a competing endogenous RNA for miR-577 to promote malignant development of colorectal cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA DLX6-AS1 functions as a competing endogenous RNA for miR-577 to promote malignant development of colorectal cancer, by F.-R. Zhou, Z.-P. Pan, F. Shen, L.-Q. Huang, J.-H. Cui, K. Cai, X.-L. Guo, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3742-3748-DOI: 10.26355/eurrev_201905_17800-PMID: 31115000" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17800.

Protective effect of the RNA-binding protein RBM10 in hepatocellular carcinoma.

OBJECTIVE: To illustrate the protective effect of RBM10 on hepatocellular carcinoma (HCC) progression and the molecular mechanism. PATIENTS AND METHODS: RBM10 levels in HCC tissues classified by tumor size and tumor node metastasis (TNM) staging were detected by quantitative real-time polymerase chain reaction (qRT-PCR) Chi-square test was conducted to reveal the relationship between RBM10 level and pathological features in HCC patients. The prognostic potential of RBM10 in HCC was assessed via the Kaplan-Meier method. Overexpression of RBM10 was achieved by transfection of LV-RBM10 in HepG2 and HCC-LM3 cells. Cell counting kit-8 (CCK-8) assay and flow cytometry were carried out to detect viability and apoptosis in HCC cells, respectively. In addition, invasive ability was assessed by transwell assay. Protein level of cleaved-caspase-3 was examined by Western blot. Regulatory effects of RBM10 on protein levels of EGFR, ERK and p-ERK were determined. RESULTS: RBM10 was downregulated in HCC tissues. Its level was markedly lower in HCC cases with larger tumor size and stage III+IV. Low level of RBM10 predicted poor prognosis in HCC patients. Overexpression of RBM10 suppressed viability and invasiveness in HCC-LM3 and HepG2 cells, but enhanced apoptotic rate and protein level of cleaved-caspase-3. EGFR was upregulated in HCC tissues, which was negatively regulated by RBM10. Overexpression of RBM10 downregulated protein levels of EGFR and p-ERK in HCC-LM3 and HepG2 cells. CONCLUSIONS: RBM10 is downregulated in HCC tissues, which is favorable to the prognosis in HCC patients. As a tumor suppressor, RBM10 attenuates proliferative and invasive abilities, but drives apoptosis in HCC cells, thus alleviating the progression of HCC.

[Recent progress in molecular targeted therapies for intrahepatic cholangiocarcinoma].

Intrahepatic cholangiocarcinoma(ICC) is the second most common primary liver cancer. The incidence of ICC has been significantly increased globally in recent years. The concealed onset of ICC usually results in late disease diagnosis. Liver resection is currently the only well-established treatment for ICC that may cure the disease, however, long-term survival rate is still unsatisfied due to the low resection rate and high recurrence rate. Local therapy combined with systemic chemotherapy is the main treatment for advanced or unresectable ICC, but the outcomes are still poor. With the in-depth understanding of the molecular mechanism of ICC and development of next-generation sequencing technology, multiple abnormal signaling pathways (RAS/MAPK, MET, EGFR) and gene mutations (FGFR2, IDH1/2) have been identified as potential therapeutic targets. Although there is still no approved targeted drugs for ICC, more than 100 clinical trials testing targeted therapy alone or in combination with chemotherapy are ongoing, among which some have shown promising application prospects. Molecular typing and personalized targeted therapy are important ways to improve the overall outcomes of ICC. This review summarized the recent advances in the targeted therapies for patients with ICC.

[WWP1 promotes cell proliferation in hepatocellular carcinoma through ubiquitin-degradation EI24].

Objective: To screen the interaction proteins of WW domain containing protein 1 (WWP1), and explore the effects of WWP1 and etoposide induced 24 (EI24) on cell proliferation in hepatocellular carcinoma (HCC). Methods: Yeast two-hybrid screening system was used to identify the interaction proteins of WWP1. The interaction was further validated by co-immunoprecipitation. WWP1 and EI24 stably over-expressing or deleted HepG2 cells were established by using the lentivirus transduction method. Colony forming assay and cell counting kit-8 (CCK8) assay were performed to identify the effects of WWP1 and EI24 on cell proliferation. In addition, the role of WWP1 in the tumorigenicity of liver cancer in vivo was examined by subcutaneous injection of different level of WWP1 expressed HepG2 into nude mice. Results: WWP1 can interact with EI24 and ubiquitin-degrade EI24 protein. The WWP1 and EI24 over-expressing or deleted HepG2 cell lines were successfully generated. Overexpression of WWP1 decreased while knockdown of WWP1 increased the protein level of EI24. The results of CCK-8 assay showed that the relative proliferation activities of WWP1 overexpressed (WWP1-OE) group and WWP1 knockdown (shWWP1) group on 36 hours were (347.00±8.15)% and (187.08±4.86)%, respectively, significantly different from (270.33±15.01)% of control group (both P<0.05). The relative proliferation activities of EI24 overexpressed (EI24-OE) group and EI24 knockdown (shEI24) group on 36 hours were (183.75±8.11)% and (317.33±9.60)%, respectively, significantly different from (270.33±15.01) % of control group (both P<0.05). The results of colony formation assay showed that the colony numbers of control group, WWP1-OE group and shWWP1 group were (52±7)/visual field (VF), (76±4)/VF, (19±3)/VF, respectively. Overexpression of WWP1 significantly increased while knockdown of WWP1 significantly decreased the colon formation ability of HepG2 cells (both P<0.05). The colon number of control group, EI24-OE group and shEI24 group were (38±4)/VF, (10±3)/VF, (69±7)/VF, respectively. Overexpression of EI24 significantly decreased while knockdown of EI24 significantly increased the colony formation ability of HepG2 cells (both P<0.05). The results of xenograft mice model showed that the tumor volumes of control, WWP1-OE, and shWWP1 group were (1 400.00±43.71)mm(3,) (2 636.67±290.45) mm(3) and (642.17±36.00)mm(3,) respectively, with significant differences (P<0.05). The tumor weight for these three groups were (1.23±0.08)g, (2.05±0.17)g, and (0.88±0.09)g, respectively, with significant differences (P<0.05). The tumor volumes of control, EI24-OE, and shEI24 group were (1 245.17±93.10)mm(3,) (662.17±60.88)mm(3) and (1 986.67±226.75)mm(3) respectively, with significant differences (P<0.05). The tumor weight for these three groups were (1.15±0.04)g, (0.85±0.02)g and (1.73±0.05)g respectively, with significant difference (P<0.05). Conclusion: WWP1 promote the cell proliferation of liver cancer through ubiquitin-degradation of EI24.

Impact of postoperative infective complications on long-term survival after liver resection for hepatocellular carcinoma.

BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection. RESULTS: Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021). CONCLUSION: Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.

Long noncoding RNA DLX6-AS1 functions as a competing endogenous RNA for miR-577 to promote malignant development of colorectal cancer.

OBJECTIVE: Recent researches have proved that long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis. The aim of this study was to investigate the exact role of lncRNA DLX6-AS1 in the development of colorectal cancer (CRC), and to explore the possible mechanism. PATIENTS AND METHODS: DLX6-AS1 expression in CRC tissues was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Function assays were conducted to detect the effect of DLX6-AS1 on the proliferation and metastasis of CRC in vitro. Furthermore, luciferase reporter gene assay and RNA immunoprecipitation assay (RIP) were used to explore the underlying mechanism of DLX6-AS1. RESULTS: DLX6-AS1 expression in CRC samples was significantly higher than that of adjacent tissues. Loss of DLX6-AS1 markedly inhibited the proliferation, migration, and invasion of CRC cells. Furthermore, luciferase reporter gene assay and RIP assay showed that DLX6-AS1 acted as a competing endogenous RNA via sponging miR-577 in CRC. CONCLUSIONS: DLX6-AS1 could promote the proliferation, migration, and invasion of CRC by sponging miR-577, which might offer a potential therapeutic target for CRC.

[Progress on surgical treatment of intrahepatic cholangiocarcinoma].

Intrahepatic cholangiocarcinoma(ICC)is a primary liver cancer with its incidence only after hepatocellular carcinoma.Liver resection is currently the only established effective treatment for patients with ICC.However,the resectability of ICC is low and the long-term survival after surgery is far from satisfactory. With the advances in the understanding of the biological characteristics and prognostic characteristics of ICC, surgical strategy and techniques have improved in recent years, and the long-term survival has also been increased. The accurate clinical diagnosis of ICC, R0 resection, routine lymphadenectomy, effective adjuvant therapy after R0 resection, and multidisciplinary treatment including re-hepatectomy for recurrent ICC are important for achieving an optimal outcome.Down-staging management for patients with unresectable ICC may provide a chance of R0 resection in some patients. Further research on the biological heterogeneity of ICC,and the improvement of surgical treatment or the establishment of new treatment methods are the main research directions in the future.

[A preliminary prospective study on the efficacy and safety of ultrasound-guided percutaneous lauromacrogol sclerotherapy in benign cystic or predominantly cystic thyroid nodules].

Objective: To investigate the efficacy and safety of percutaneous lauromacrogol injection (PLI) in treatment of cystic or predominantly cystic thyroid nodules. Methods: A total of 114 cystic thyroid nodules and 61 predominantly cystic thyroid nodules with pain or uncomfort or aesthetic complaints were offered PLI. Therapeutic success rates and side effects were evaluated. From October 2012 to December 2015,114 patients with cystic thyroid nodules and 61 with predominantly cystic thyroid nodules with pain or uncomfortable or aesthetic complaints at the outpatient clinic of the First Affiliated Hospital of Wenzhou Medical University were offered percutaneous lauromacrogol sclerotherapy. Cytological results were benign. This study was a prospective trial. Ultrasonography sound examination was performed in all patients before treatment. The baseline data of all the patients and the data of the patients examined at the follow-up of 1, 3, 6 and 12 months were analyzed. Therapeutic success rate (nodule volume reduction >50%) and safety were observed. The data of nodule volume reduction ratio and the function of thyroid were normal distribution and analyzed by Mann-Whitney test and t test. The data of nodule volume, symptoms score and cosmetic score were skewed distribution, which were indicated with median and analyzed by nonparamentic test. Results: The mean volume of the cystic thyroid nodules was reduced from 12.5 cm(3) before PLI to 0.2 cm(3) at 12 months after PLI (χ(2)=266.175, P<0.001), with a therapeutic success rate of 100%, and the mean volume of the predominantly cystic thyroid nodules was reduced from 10.5 cm(3) before PLI to 2.0 cm(3) at 12 months after PLI (χ(2)=203.122, P<0.001) with a therapeutic success rate of 93.4%(57/61). Pressure symptom score and cosmetic grade were significantly improved at 12 months after PLI in patients with cystic or predominantly cystic thyroid nodules. Pressure symptom score and cosmetic grade in patients with cystic thyroid nodules were Z=-6.126 and Z=-13.735, respectively; pressure symptom score and cosmetic grade in patients with predominantly cystic thyroid nodules were Z=-3.126 and Z=-7.212, respectively (all P<0.001) . There no significant difference in the thyroid functions before and after PLI in two groups of patients (all P>0.05) . The side effects of PLI were mild. Conclusion: PLI is a safe and effective alternative to treat benign cystic or predominantly cystic thyroid nodules.

Mycobacterium Tuberculosis infection among the elderly in 20 486 rural residents aged 50-70 years in Zhongmu County, China.

OBJECTIVES: Elderly individuals in rural China have been known to be at increased risk of contracting tuberculosis (TB) and developing active disease. This study aims to estimate the burden of mycobacterium tuberculosis (MTB) infection and to identify potential targeted subgroups for infection control. METHODS: As part of the investigation of an interventional study, 50- to 70-year-old rural residents in Zhongmu County were targeted for MTB infection testing using QuantiFERON-TB Gold In-Tube (QFT). Questionnaires and physical examinations were conducted to acquire their demographic information and health status. RESULTS: A total of 20 486 individuals were included in the analysis. The prevalence of QFT positivity was 20.79% (4259/20 486) and 50 participants (0.24%) had indeterminate results. A positive dose-response relation was found for QFT positivity with smoking intensity. Compared with non-drinkers, the risk of MTB infection was lower among participants with moderate alcohol consumption (<10 g/day) with adjusted odds ratio (OR) of 0.82 (95% CI 0.71-0.94). In addition, gender of male, with a history of previous TB or silicosis, and hepatitis B/C virus infection were associated with increased risk of MTB infection. An indeterminate QFT result was related to being underweight (adjusted OR 3.18; 95% CI 1.09-9.26). CONCLUSIONS: Our results indicate a high burden of MTB infection among the elderly in this rural area. Smokers, individuals with a history of previous TB or silicosis, and those with hepatitis B/C virus infection should be prioritized for MTB infection control to reduce the risk of disease development from a new infection.