miR-4709 overexpression facilitates cancer proliferation and invasion via downregulating NR3C2 and is an unfavorable prognosis factor in colon adenocarcinoma.

To date, microRNA-4709 (miR-4709) has not been studied in colon adenocarcinoma (COAD) on the basis of experiments. In our study, we aimed to investigate the biological roles and clinical significance of miR-4709 in COAD. The expression difference between miR-4709 and NR3C2 was measured based on The Cancer Genome Atlas database and cells. Kaplan-Meier and logrank tests were applied to determine the overall survival (OS) differences according to the miR-4709 and NR3C2 expression levels. To measure whether the miR-4709 level was associated with COAD cell growth, migration, and invasion, we respectively conducted 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, and transwell assays. A luciferase reporter assay was applied to confirm the relationship between miR-4709 and its predicted target. High expression of miR-4709 was found in COAD tissues and cells. The OS rate in the miR-4709 low expression group was significantly higher than that in the miR-4709 high expression group. Univariate and multivariate analyses exhibited that miR-4709 expression was an independent adverse prognostic factor. Exogenous miR-4709 overexpression promoted proliferation, migration, and invasion of LOVO and SW480 cells. Bioinformatics analysis and luciferase assay demonstrated that miR-4709 directly binds to the 3'-untranslated region of NR3C2. NR3C2 was lowly expressed in COAD and high expression of NR3C2 had a better prognosis compared with that in the low expression of NR3C2. Correlation analysis showed that there is a close association between the level of expression of NR3C2 and miR-4709. Accordingly, miR-4709 may function as an oncogene in COAD and provide a preclinical proof for candidate management to target new miR-4709-NR3C2 signaling for COAD therapy.

Association of HMGB1 Gene Polymorphisms with Risk of Colorectal Cancer in a Chinese Population.

BACKGROUND Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. More advanced work is required in the detection of biomarkers for CRC susceptibility and prognosis. High-mobility group box-1 (HMGB1) is an angiogenesis-related gene reported to be associated with the development of CRC. The direct evidence of HMGB1 gene polymorphisms as biomarkers for CRC has not been reported previously. MATERIAL AND METHODS A total of 240 CRC patients and 480 healthy controls were periodically enrolled. DNA was extracted from blood specimens. The distributions of SNPs of HMGB1 were determined by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS In this case-control study, we observed a significant association between overall CRC risk and SNP rs2249825 (CG vs. CC and GG vs. CC). Participants carrying both rs2249825 CG (OR, 2.67; 95% CI, 1.89 to 3.78) and rs2249825 GG genotypes (OR, 2.32; 95% CI, 1.13 to 4.73) had a significantly increased risk of developing CRC compared to those carrying GG genotype. rs2249825 was associated with the risk of CRC in the dominant model but not in the recessive model. However, we found no significant differences in the rs1412125 or rs1045411 polymorphisms in the HMGB1. Advanced analyses showed that the number of rs2249825 G alleles showed a significant relationship with risk of CRC. CONCLUSIONS Our results show an association between HMGB1 rs2249825 SNP and CRC incidence in the Chinese Han population. However, population-based studies with more subjects and prognostic effects are needed to verify the association of HMGB1 SNPs with CRC susceptibility, severity, and long-term prognosis.

Diagnostic value of computed tomography scanning in differentiating malignant from benign solitary pulmonary nodules: a meta-analysis.

An early diagnosis of lung cancer is crucial for early treatment and management. The objective of this systematic review was to assess the overall diagnostic accuracy of chest computed tomography (CT) scanning in differentiating malignant from benign solitary pulmonary nodules (SPNs) with meta-analysis. The PubMed and China National Knowledge Infrastructure (CNKI) database were searched for eligible studies published up to March 2014. The sensitivity, specificity, and other measures of accuracy of chest CT scanning in the diagnosis of SPNs were pooled along with 95 % confidence intervals (CI). Summary receiver operating characteristic (ROC) curves were used to summarize overall test performance. Thirty-two studies met our inclusion criteria. The summary estimates for chest CT scanning in the diagnosis of SPNs in the meta-analysis were as follows: pooled sensitivity, 0.89 (95 % CI, 0.88 to 0.91); pooled specificity, 0.70 (95 % CI, 0.68 to 0.73); positive likelihood ratio, 2.88 (95 % CI, 2.46 to 3.37); negative likelihood ratio, 0.16 (95 % CI, 0.12 to 0.21); and diagnostic odds ratio, 23.83 (95 % CI, 16.18 to 35.11). The results indicate that CT scanning has relatively high sensitivity and moderate specificity for the diagnosis of SPNs. Given the low cost and growing prevalence of the technology, CT scanning should be recommended as the initial test for the evaluation of SPNs.

Incidence and risk factors for pulmonary hemorrhage after percutaneous CT-guided pulmonary nodule biopsy: an observational study.

To evaluate the current incidence of pulmonary hemorrhage and the potential factors contributing to its increased risk after percutaneous CT-guided pulmonary nodule biopsy and to summarize the technical recommendations for its treatment. In this observational study, patient data were collected from ten medical centers from April 2021 to April 2022. The incidence of pulmonary hemorrhage was as follows: grade 0, 36.1% (214/593); grade 1, 36.8% (218/593); grade 2, 18.9% (112/593); grade 3, 3.5% (21/593); and grade 4, 4.7% (28/593). High-grade hemorrhage (HGH) occurred in 27.2% (161/593) of the patients. The use of preoperative breathing exercises (PBE, p =0.000), semiautomatic cutting needles (SCN, p = 0.004), immediate contrast enhancement (ICE, p =0.021), and the coaxial technique (CoT, p = 0.000) were found to be protective factors for HGH. A greater length of puncture (p =0.021), the presence of hilar nodules (p = 0.001), the presence of intermediate nodules (p = 0.026), a main pulmonary artery diameter (mPAD) larger than 29 mm (p = 0.015), and a small nodule size (p = 0.014) were risk factors for high-grade hemorrhage. The area under the curve (AUC) was 0.783. These findings contribute to a deeper understanding of the risks associated with percutaneous CT-guided pulmonary nodule biopsy and provide valuable insights for developing strategies to minimize pulmonary hemorrhage.

Pneumothorax after percutaneous CT-guided lung nodule biopsy: a prospective, multicenter study.

Background: Pneumothorax is a common complication induced by computed tomography (CT)-guided percutaneous needle biopsy, with a frequency of 17-40.4%. It remains debatable how to predict and prevent the occurrence of post-biopsy pneumothorax. In a real-world setting, we investigated the characteristics associated with pneumothorax in primary lung nodule biopsy. Methods: This clinical registry cohort study recorded patients with newly diagnosed pulmonary nodules from 10 medical centers from April 2021 to April 2022, and the data were input into the electronic data capture (EDC) system. The eligibility criteria for participants included being within the age range of 18 to 80 years and expressing a willingness to undergo percutaneous puncture biopsy, among other requirements. Conversely, the exclusion criteria included an inability to cooperate throughout the biopsy process and the emergence of new health issues during the study duration resulting in attendance delays, among other factors. This study collected data from 924 patients, out of which 593 were included after exclusion. The essential characteristics, imaging features of pulmonary nodules, and technical factors associated with percutaneous biopsy were recorded. T-tests or one-way analysis of variance (ANOVA) were performed for continuous variables and Pearson's χ2 test, likelihood ratio, or Fisher's exact test were applied for categorical variables for comparison as appropriate, followed by multivariate logistic regression. Results: The overall incidence of pneumothorax was 13.0% (77/593), among which timely pneumothorax was 10.3% (61/593), delayed pneumothorax was 2.7% (16/593), and the rate of chest tube placement was 3.4% (20/593). There was no significant difference in the incidence of pneumothorax in a needle size range of 16-19 G (P=0.129), but the incidence of pneumothorax was lower with 17 G needles than with 18 G. An increased morbidity of pneumothorax was correlated with age (P=0.003), emphysema (P=0.006), and operation time (P=0.002). There was no significant increase in the incidence of pneumothorax between 1 or 2 passes through the pleura (P=0.062). However, multiple pleural passes (3 times) increased the chances of pneumothorax significantly (P=0.022). These risk factors have a certain clinical value in predicting the incidence of post-biopsy pneumothorax, and the area under the curve (AUC) was 0.749. Conclusions: The most common post-biopsy complication, pneumothorax, was managed conservatively in most cases. A maximum of two pleural passes does not increase the incidence of pneumothorax, and the 17 G needle is more suitable for percutaneous biopsy of pulmonary nodules in the real world.

[Application of three-dimensional endoanal and endorectal ultrasound in the diagnosis of anorectal fistula].

OBJECTIVE: To evaluate the efficacy of three-dimensional anal and endorectal ultrasound in identifying the internal opening and tracing the tract of the anorectal fistula. METHODS: From November 2008 to January 2010, 127 patients suffering anorectal fistula were managed with three-dimensional endoanal and endorectal ultrasound. The internal opening, the tract of the fistula and fistula trace were identified by the ultrasonography with three-dimensional imaging. All results were confirmed and compared with findings from the operation. RESULTS: The internal opening of the fistula was specified in 116 patients, the accuracy rate was 91.3% (116/127). The internal opening of the fistula was located above the dentate line in 112 patients, and located in rectal ampulla in 4 patients. The main fistula tract was identified in all the patients, the accuracy rate was 100%. In this group, the fistula tunneled as follows: trans-sphincteric in 47 patients, intersphincteric in 75 cases, supra sphincteric in 2 cases, extra sphincteric in 3 patients. Secondary extension was found in 37 patients, the accuracy rate was 100% (37/37). CONCLUSIONS: Three-dimensional anal and endorectal ultrasound is an effective way for localizing the internal opening and the tract of anorectal fistula. It can provide valuable information for curative operation.

A retrospective analysis of the risk factors associated with systemic air embolism following percutaneous lung biopsy.

In the present study, the risk factors for systemic air embolism as a complication of percutaneous CT-guided lung biopsy were explored. Data from 2,026 percutaneous CT-guided lung biopsy procedures were retrospectively analyzed. All cases were divided into a concurrent air embolism group and a control group, depending on whether air embolism occurred during the puncture process. A systemic air embolism was confirmed when CT values <-200 Hounsfield units were observed in two sequential images. A total of 19 cases (0.9%) of air embolism were detected among the 2,026 patients subjected to percutaneous CT-guided lung biopsy procedures. The most frequently detected embolism site was the left ventricle (89.5%). Only 3 cases (15.8%) were accompanied by obvious clinical symptoms. The results indicated that a puncture location above the level of the left atrium and coughing during the procedure significantly altered the likelihood of embolism developing (P=0.002 and P=0.014 vs. control, respectively). In conclusion, a puncture lesion above the level of the left atrium and coughing during the procedure may be risk factors for air embolism development.

Downregulated let-7d positively stimulates rectum adenocarcinoma cell malignant biological behaviors by upregulating ATP binding cassette subfamily C member 2.

BACKGROUND: Let-7d has been reported to serve as a tumor suppressor in numerous cancers, however, the function in rectum adenocarcinoma has not been illuminated. In this study, we aimed to explore whether let-7d functions in rectum adenocarcinoma and its functional significance links to ATP binding cassette subfamily C member 2 (ABCC2). METHODS: The expression patterns of let-7d and ABCC2 were gained from TCGA database. Then, cell proliferation, invasion and migration assays were conducted to detect the influence on rectum adenocarcinoma cells behaviors after over-expression of let-7d. Subsequently, the potential target gene of let-7d was predicted and identified through bioinformatics prediction analysis and luciferase reporter assay. Analyses against prognostic value and independent predictor were acquired from Kaplan-Meier, Univariate and Multivariate analysis of Cox regression. Finally, con-transfection experiments were performed to investigate let-7d/ABCC2 pairs function on rectum adenocarcinoma cells after co-transfected with let-7d mimic and si-ABCC2. mRNA and protein levels were assessed by reverse transcription quantitative polymerase chain reaction (qRT-PCR) and western blot. RESULTS: The data from TCGA indicated that let-7d was down-regulated in rectum adenocarcinoma samples, whilst ABCC2 was showed a trend of high expression and its overexpression hinted to worse overall survival of rectum adenocarcinoma patients. Cells proliferation, invasion and migration properties were restrained after over-expression of let-7d in SW837 cells. Further investigations showed that over-expression of let-7d induced the inhibitory effect on SW837 cells proliferative, migrant and invasive capacities was augmented by silencing ABCC2. CONCLUSIONS: All results in this study indicated that up-regulation of let-7d could suppress SW837 cells growth, invasion and migration abilities by reducing ABCC2 expression, providing a new insight into molecular mechanism of let-7d/ABCC2 as a significant mediator for tumor progression and development of rectum adenocarcinoma.

[Characteristics and Source Apportionment of Ambient Volatile Organic Compounds in Winter in Jincheng].

Air samples were collected and analyzed by GC-MS to investigate the component characteristics of volatile organic compounds (VOCs) in winter in Jincheng. PMF, ratio analysis, and the backward trajectory model were used to investigate sources of VOCs. Ozone formation potential and secondary organic aerosol formation potential were calculated, in order to analyze the environmental implications of detected VOCs. Results showed that the average concentration of VOCs was 93.35 µg·m-3 in Jincheng, with the most abundant component being alkane (52.91 µg·m-3 and 56.68% of total VOCs). Based on PMF analysis, five sources of ambient VOCs in Jincheng were identified, namely industrial emission sources (33.71%), fuel combustion sources (30.27%), vehicle emissions (26.28%), solvent evaporation sources (9.00%), and plant emission sources (0.74%). Ratios of B/T and i-pentane/n-pentane were 1.58±0.68 and 2.07±0.43, indicating that VOCs were derived from the mixture of road and coal combustion sources. Clustered analysis of the air mass backward trajectory showed that three air masses cluster, which were accounting for 50%, 25% and 25% of the total back trajectories respectively, all came from the northwest, and industrial pollution from the northwest might therefore significantly influence VOCs in Jincheng. With low wind speed (<3 m·s-1), the air quality index, concentration of total VOCs, and contribution rate of vehicle emissions were 143, 162.48 µg·m-3, and 46.16%, respectively, higher than values at faster wind speeds (3-6.9 m·s-1). Ozone formation potential and secondary organic aerosol formation potential of aromatic hydrocarbons, which had the highest formation potential, were 98.89 µg·m-3 and 1.21 µg·m-3, respectively, accounting for 37.28% and 97.01% of total formation potential. To reduce the pollution of VOCs in Jincheng, it is important to control industrial emissions, vehicle emissions, and fuel combustion emissions.

Anticancer effects of 10-hydroxycamptothecin induce apoptosis of human osteosarcoma through activating caspase-3, p53 and cytochrome c pathways.

In order to evaluate the anticancer effect of 10-hydroxycamptothecin (HCPT) in terms of inducing the apoptosis of human osteosarcoma cells, its apoptosis-inducing molecular mechanisms were investigated. In the present study, the anticancer effects of HCPT were revealed to result in suppressed cell viability, increased cytotoxicity, the induction of apoptosis and an augmented apoptotic nucleolus of human osteosarcoma cells. MG-63 cells were cultured with HCPT (0, 20, 40 and 80 nM) for 24 and 48 h. An MTT assay and a lactate dehydrogenase assay were used to analyze the anticancer effect of HCPT on cell viability and cytotoxicity in MG-63 cells. MG-63 cell apoptosis, and caspase-9 and caspase-3 activity levels were evaluated using flow cytometry and an ELISA. Western blot analysis was used to detect the protein expression levels of p53, poly (ADP-ribose) polymerase-1 (PARP-1), cytochrome c and B cell lymphoma-2 (Bcl-2) in MG-63 cells. The anticancer effects of HCPT were demonstrated to significantly activate the protein expression of p53, PARP-1 and cytochrome c, and suppress Bcl-2 protein expression and promote the activity of caspase-9 and caspase-3 in human osteosarcoma cells. In conclusion, the anticancer effects of HCPT appear to induce the apoptosis of human osteosarcoma cells through the activation of the caspase-3, p53 and cytochrome c pathways.

Mitochondrial genome of a spontaneous multiple myeloma bone cancer model mouse C57BL/KaLwRij strain.

We sequenced the complete mitochondrial genome of a multiple myeloma bone cancer model mouse C57BL/KaLwRij strain for the first time. The total length of the mitogenome was 16,297 bp, with 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. This mitochondrial genome sequence contains 127 SNPs compared with the house mouse reference sequence.

Ginkgetin exerts growth inhibitory and apoptotic effects on osteosarcoma cells through inhibition of STAT3 and activation of caspase-3/9.

Osteosarcoma is composed of tumor osteoblasts and bone-like tissues, with malignant tumors originating from osteogenesis organization. Osteosarcoma is a primary malignant bone tumor. Invasion and metastasis of osteosarcoma affect the prognosis of patients. However, effective therapeutic treatments remain to be identified. The aim of the present study was to investigate the possible inhibitory and apoptotic effects of ginkgetin in osteosarcoma cells. 3.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were used to determine the effect ginkgetin exerted on the growth of osteosarcoma cells. Flow cytometry was used to determine cell apoptosis. STAT3 protein expression and activation of caspase-3/9 were measured using western blot analysis and the MTT and LDH assays, respectively. The results showed that ginkgetin inhibited cell growth and induced cell cytotoxicity in osteosarcoma cells in a dose-dependent manner. Treatment with ginkgetin significantly activated the apoptosis of osteosarcoma cells in a concentration-dependent manner. The anticancer activity of ginkgetin significantly inhibited STAT3 and promoted caspase-3/9 activation in osteosarcoma cells. The findings demonstrated that ginkgetin exerts growth inhibitory and apoptotic effects on osteosarcoma cells through the inhibition of STAT3 and activation of caspase-3/9.

Effect of lipiodol and methylene blue on the thoracoscopic preoperative positioning.

The aim of this study was to compare and analyze the site-specific accuracy of mixture of lipiodol and methylene blue (MLM) (0.6 ml, 1:5) and pure methylene blue (0.5 ml) on the rabbit lungs. In this study, CT-guided percutaneous injection of MLM and methylene blue. Compare the staining degree by biopsy of lung tissue. Use 4 points system to evaluate the site-specific accuracy at 6h and 24 h after injection. For MLM, evaluate its radiopacity by radiation. When evaluate the positioning, 2 points mean acceptable, 3 points mean excellent. The results indicated that the staining range of MLM is obvious less than that of methylene blue (0.6 vs. 1.0 cm, P<0.01), but the staining capacity of MLM is higher than that of methylene blue (2.8 vs. 2.2, P = 0.01). About the staining abilities which are evaluated as excellent, MLM group accounts for 81%, methylene blue group accounts for 38% (P = 0.011). About the radiopacity which are evaluated as acceptable or excellent, MLM group accounts for 62%. With good direct vision, the suitable positioning rate of MLM can be 100%, which is better than that of methylene blue. In conclusion, percutaneous injection of MLM can be used to lung positioning. The result shows that use MLM is better than only using methylene blue. But it is necessary to do the investigation in human beings in order to confirm the feasibility of its clinical application.

Accessory spleen appearing as an intrasplenic pseudo-tumoral mass: A rare case report.

The current study presents a rare case of an accessory spleen that manifested as a solid intrasplenic pseudotumor. The affected patient was previously healthy. Upon examination with computed tomography (CT), an ovoid, soft-tissue mass of ~4.1 cm in diameter was found on the upper pole of the spleen. Biochemical indices, such as blood routine and coagulation tests, and tumor marker analysis, revealed no abnormalities. Another CT scan was performed, but this failed to indicate whether the mass was benign or malignant. Therefore, the lesion was resected along with the spleen by laparoscopic surgery. The resected sample was subject to pathological examinations for final validation, and was finally diagnosed as an accessory spleen. The patient was followed up for six months with no signs of recurrence.

Sclareol, a plant diterpene, exhibits potent antiproliferative effects via the induction of apoptosis and mitochondrial membrane potential loss in osteosarcoma cancer cells.

The objective of the current study was to evaluate the antiproliferative activity of sclareol against MG63 osteosarcoma cells. A 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay was used to evaluate the cell viability of cells following treatment with sclareol. The extent of cell death induced by sclareol was evaluated using a lactate dehydrogenase (LDH) assay. The effect of sclareol on cell cycle progression and mitochondrial membrane potential (ΛΨm) was evaluated with flow cytometry using the DNA­binding fluorescent dyes propidium iodide and rhodamine­123, respectively. Fluorescence microscopy was used to detect the morphological changes in the MG63 osteosarcoma cancer cells and the appearance of apoptotic bodies following sclareol treatment. The results revealed that sclareol induced dose­ and time­dependent growth inhibition of MG63 cancer cells with an IC50 value of 65.2 µM following a 12­h incubation. Furthermore, sclareol induced a significant increase in the release of LDH from MG63 cell cultures, which was much more pronounced at higher doses. Fluorescence microscopy revealed that sclareol induced characteristic morphological features of apoptosis and the appearance of apoptotic bodies. Flow cytometry revealed that sclareol induced G1­phase cell cycle arrest, which showed significant dose­dependence. Additionally, sclareol induced a progressive and dose­dependent reduction in the ΛΨm. In summary, sclareol inhibits the growth of osteosarcoma cancer cells via the induction of apoptosis, which is accompanied by G1­phase cell cycle arrest and loss of ΛΨm.

New furo3,2-hisochroman from the mangrove endophytic fungus Aspergillus sp. 085242 / 中国天然药物

Four new compounds, asperisocoumarin G (1), asperisocoumarin H (2), (±)-asperisocoumarin I [(±)-3], along with the known pergillin (4) and penicisochroman L (5) were isolated from a mangrove endophytic fungus Aspergillus sp. 085242 by further chemical investigation. The structures of the new compounds, including their absolute configurations, were established by analysis of HR-ESI-MS and NMR spectroscopic data, and ECD calculation. Asperisocoumarins G-I (1-3) were new isocoumarins belonging to the class of furo[3, 2-h]isocoumarins which are rarely found in natural sources. All of the isolated compounds were evaluated for their α-glucosidase inhibitory effects, and compounds 1 and 4 showed moderate α-glucosidase inhibitory activity, respectively. In an antimicrobial test, the racemate of 3 showed antibacterial activity against Salmonella.