Epidemiology and Prognostic Nomogram for Predicting Long-Term Disease-Specific Survival in Patients With Pancreatic Carcinoid Tumor: A SEER-Based Study.

OBJECTIVES: Pancreatic carcinoid tumor (PCT) is described as a malignant form of carcinoid tumors. However, the epidemiology and prognostic factors for PCT are poorly understood. MATERIALS AND METHODS: The data of 2447 PCT patients were included in this study from the Surveillance, Epidemiology, and End Results database and randomly divided into a training cohort (1959) and a validation cohort (488). The epidemiology of PCT was calculated, and independent prognostic factors were identified to construct a prognostic nomogram for predicting long-term disease-specific survival (DSS) among PCT patients. RESULTS: The incidence of PCT increased remarkably from 2000 to 2018. The 1-, 5-, and 10-year DSS rates were 96.4%, 90.3%, and 86.5%, respectively. Age at diagnosis, stage, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors to construct a prognostic nomogram. The C -indices; area under the receiver operating characteristic curves for predicting 1-, 5-, and 10-year DSS, and calibration plots of the nomogram in both cohorts indicated a high discriminatory accuracy, preferable survival predictive ability, and optimal concordances, respectively. CONCLUSIONS: The incidence of PCT has increased rapidly since 2000. In addition, we established a practical, effective, and accurate prognostic nomogram for predicting the long-term DSS of PCT patients.

Synthesis, antibacterial activity, and 3D-QASR studies of matrine-indole derivatives as potential antibiotics.

Matrine and indole have antibacterial, anticancer, and other biological activities, in order to develop new antibiotics to solve the problem of multi-drug resistant bacteria. In this paper, we synthesized a series of 29 novel matrine derivatives as potential drug candidates by combining indole analogs and matrine. The antibacterial activity of these compounds was evaluated through minimum inhibitory concentration (MIC) assays against five bacterial strains (S. aureus, C. albicans, P. acnes, P. aeruginosa, and E. coli). The obtained results demonstrated promising antibacterial efficacy, particularly for compounds A20 and A18, which exhibited MICs.au values of 0.021 and 0.031 mg/ml, respectively, against S. aureus. Moreover, compounds A20 and A27 displayed remarkable MICc.al values of 2.806 and 4.519 mg/ml, respectively, against C. albicans, surpassing the performance of the clinical antibiotic penicillin G sodium (0.0368 mg/ml) and fluconazole (4.849 mg/ml). These findings underscore the significant bacteriostatic activity of the matrine derivatives. Furthermore, to gain a deeper understanding 3D-QSAR modeling was employed, revealing the critical influence of steric structure, charge distribution, hydrophobic interactions, and hydrogen bonding within the molecular structure on the bacteriostatic activity of the compounds. Additionally, molecular docking simulations shed light on the interaction between compound A20 and bacterial proteins, highlighting the involvement of hydrogen bonding, hydrophobic interactions, and π-π conjugation in the formation of stable complexes that inhibit the normal functioning of the proteins. This comprehensive analysis provided valuable insights into the antibacterial mechanism of the novel matrine derivatives, offering theoretical support for their potential application as antibiotics.

Chrysophanol induces apoptosis and ferroptosis of gastric cancer cells by targeted regulation of mTOR.

Programmed cell death (PCD) induction is a promising strategy for killing gastric cancer cells. In this study, we investigated the effects of chrysophanol on apoptosis and ferroptosis in gastric cancer cells. Chrysophanol in concentrations ranging from 0 to 100 µM were used to treat GES-1, HGC-27 and AGS cells. Cell counting kit-8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, JC-1 probe insertion, dihydroethidium staining and western blotting were performed. The effects of chrysophanol on gastric cancer cells were evaluated in vivo using a xenograft mouse model. Chrysophanol had no cytotoxic effects on GES-1 cells. Chrysophanol with concentrations higher than 25 µM inhibited gastric cancer cell colony formation and proliferation. Chrysophanol induces gastric cancer cell apoptosis in a dose-dependent manner, accompanied by mitochondrial membrane potential dysfunction and cytochrome c release. Additionally, chrysophanol increased the levels of reactive oxygen species, total iron, and Fe2+ in HGC-27 and AGS cells, in a dose-dependent manner. Treatment of cells with the ferroptosis inhibitor ferrostatin-1 attenuated the effects of chrysophanol on cell survival and the expression of ferroptosis markers SLC7A11 and GPX4. Screening by GEO software indicated that the mTOR signalling pathway is possibly regulated by chrysophanol. Furthermore, mTOR overexpression significantly reversed the inhibitory effects of chrysophanol on gastric cancer cells. In gastric cancer xenograft mouse models, chrysophanol treatment inhibited tumour growth and downregulated SLC7A11 and GPX4. Chrysophanol induces apoptosis and ferroptosis, making it a potential candidate for killing gastric cancer cells. The beneficial effects of chrysophanol may be attribute to the targeted regulation of mTOR.

Risedronate-functionalized manganese-hydroxyapatite amorphous particles: A potent adjuvant for subunit vaccines and cancer immunotherapy.

The cGAS-STING pathway and the Mevalonate Pathway are druggable targets for vaccine adjuvant discovery. Manganese (Mn) and bisphosphonates are known to exert adjuvant effects by targeting these two pathways, respectively. This study found the synergistic potential of the two pathways in enhancing immune response. Risedronate (Ris) significantly amplified the Mn adjuvant early antibody response by 166-fold and fortified its cellular immunity. However, direct combination of Mn2+ and Ris resulted in increased adjuvant toxicity (40% mouse mortality). By the combination of doping property of hydroxyapatite (HA) and its high affinity for Ris, we designed Ris-functionalized Mn-HA micro-nanoparticles as an organic-inorganic hybrid adjuvant, named MnHARis. MnHARis alleviated adjuvant toxicity (100% vs. 60% survival rate) and exhibited good long-term stability. When formulated with the varicella-zoster virus glycoprotein E (gE) antigen, MnHARis triggered a 274.3-fold increase in IgG titers and a 61.3-fold surge in neutralization titers while maintaining a better long-term humoral immunity compared to the aluminum adjuvant. Its efficacy spanned other antigens, including ovalbumin, HPV18 VLP, and SARS-CoV-2 spike protein. Notably, the cellular immunity elicited by the group of gE + MnHARis was comparable to the renowned Shingrix®. Moreover, intratumoral co-administration with an anti-trophoblast cell surface antigen 2 nanobody revealed synergistic antitumor capabilities. These findings underscore the potential of MnHARis as a potent adjuvant for augmenting vaccine immune responses and improving cancer immunotherapy outcomes.

Dynamic changes of serum miR-105-3p expression and prognostic value evaluation of postoperative thyroid cancer.

Thyroid cancer (TC) originates from thyroid epithelial cells and is one of the common malignant tumors in the endocrine system. The aim of our study was to explore the dynamic changes of serum miR-105-3p expression after TC surgery and its correlation with clinicopathological manifestations, and evaluate its clinical value as a potential biomarker after surgery. A total of 100 TC patients were selected as the research objects. To detect serum miR-105-3p in patients and its correlation with tumor pathological characteristics and the dynamic changes of postoperative serum miR-105-3p in patients to evaluate its prognostic value as a potential biomarker. Serum miR-105-3p increases in patients with well-differentiated TC and lymph node metastasis; Serum miR-105-3p gradually decreases after surgery, and there is a significant difference between 4 days after surgery and before surgery,  serum miR-105-3p level can significantly distinguish between patients with poor prognosis and good prognosis within 2 years after the operation, and it can predict the improvement of the prognosis of TC after surgery. The level of serum miR-105-3p is closely related to tumor differentiation and lymph node metastasis in TC patients. Its level gradually decreases with the passage of time after surgery. It has a good diagnostic value for the prognosis of TC after surgery and is expected to become a TC surgery. Potential biomarkers for post-diagnosis.

Dynamic changes of serum miR-105-3p expression and prognostic value evaluation of postoperative thyroid cancer.

OBJECTIVE: To explore the dynamic changes of serum miR-105-3p expression after thyroid cancer surgery and its correlation with clinicopathological manifestations and to evaluate its clinical value as a potential biomarker after surgery. METHODS: A total of 100 thyroid cancer patients admitted to Shaanxi Provincial People's Hospital from November 2020 to August 2021 were selected as the research objects. The aim was to detect the expression of serum miR-105-3p in patients and its correlation with tumor pathological characteristics (pathological type, tumor differentiation, TNM stage, lymph node metastasis), and to detect the dynamic changes of postoperative serum miR-105-3p in patients to evaluate its prognostic value as a potential biomarker. RESULTS: The level of serum miR-105-3p increases in patients with well-differentiated thyroid cancer and lymph node metastasis; the level of serum miR-105-3p gradually decreases with the passage of time after surgery, and there is a significant difference between 4 d after surgery and before surgery; serum miR-105-3p level can significantly distinguish between patients with poor prognosis and good prognosis within 2 years after the operation, and it can predict the improvement of the prognosis of thyroid cancer after surgery. CONCLUSIONS: The level of serum miR-105-3p is closely related to the degree of differentiation and lymph node metastasis in patients with thyroid cancer. Its level gradually decreases with the passage of time after surgery. It has a good diagnostic value for the prognosis of thyroid cancer after surgery and when it is expected to become a thyroid cancer surgery. Potential biomarkers for post-diagnosis.

MiR-128-1-5p inhibits cell proliferation and induces cell apoptosis via targeting PRKCQ in colorectal cancer.

Previous studies have indicated that miR-128 was downregulated in a variety of cancers including colorectal cancer (CRC). However, the role and the underlying molecular mechanisms of miR-128 in CRC still remain largely unknown. The aim of this study was to investigate the level of miR-128-1-5p in CRC patients and to explore both the effects and regulatory mechanisms of miR-128-1-5p in the malignancy of CRC. Real-time PCR and western blot were used to analyze the expression levels of miR-128-1-5p and the direct downstream target protein tyrosine kinase C theta isoform (PRKCQ). Cell Counting Kit-8, clone formation, TUNEL apoptosis assays, and subcutaneous tumor model were performed to investigate the malignant ability of colon cancer cells. A luciferase assay was performed to explore whether miR-128-1-5p could directly bind to 3'-UTR region of PRKCQ. In the present study, we detected the decreased expression and clinical significances of miR-128-1-5p in colorectal cancer tissues and cell lines. Functional experiments revealed that miR-128-1-5p inhibited cell proliferation and induced cell apoptosis and that PRKCQ was identified as a target of miR-128-1-5p and involved in miR-128-1-5p-mediated proliferation and apoptosis. In conclusion, our results showed that miR-128-1-5p reduced CRC growth by modulating PRKCQ expression and is a possible new therapeutic target for patients with CRC.

A poly(dimethylsiloxane)-based solid-phase microchip platform for dual detection of Pseudorabies virus gD and gE antibodies.

Pseudorabies caused by pseudorabies virus (PRV) infection is still a major disease affecting the pig industry; its eradication depends on effective vaccination and antibody (Ab) detection. For a more rapid and accurate PRV detection method that is suitable for clinical application, here, we established a poly(dimethylsiloxane)-based (efficient removal of non-specific binding) solid-phase protein chip platform (blocking ELISA) for dual detection of PRV gD and gE Abs. The purified gD and gE proteins expressed in baculovirus were coated into the highly hydrophobic nanomembrane by an automatic spotter, and the gray values measured by a scanner were used for the S/N (sample/negative) value calculation (gD and gE Abs standard, positive: S/N value ≤0.6; negative: S/N value >0.7; suspicious: 0.6 < S/N ≤ 0.7). The method showed an equal sensitivity in the gD Ab test of immunized pig serum samples compared to the neutralization test and higher sensitivity in the gE Ab test compared to the commercial gE Ab detection kit. In the clinical evaluation, we found an agreement of 100% (122/122) in the gD Ab detection compared to the neutralization test and an agreement of 97.5% (119/122) in the gE Ab detection compared to the commercial PRV gE Ab detection kit. In summary, the protein chip platform for dual detection of PRV gD and gE Abs showed high sensitivity and specificity, which is suitable for PRV immune efficacy evaluation and epidemic monitoring.

Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell Senescence.

Background: Lung cancer has considerably high mortality and morbidity rate. Lung adenocarcinoma (LUAD) tissues highly express lamin B1 (LMNB1), compared with normal tissues. In this study, we knocked down LMNB1 in LUAD cells A549 and NCI-1299 to explore the effect of its inhibition on the proliferation of cells and the potential mechanism. Methods: Using bioinformatics methods, we analyzed the specificity of LMNB1 mRNA expression level in LUAD and its effect on prognosis from TCGA data. SiRNAs were used to knock down LMNB1 in the A549 cell line, and the knockdown effect was identified by western blotting and qRT-PCR. Through CCK8 cell proliferation assay, wound healing assay, TRAP, cloning formation Assay, DNase I-TUNEL assay, ATAC-seq, immunofluorescence, FISH, in vivo mouse xenograft studies, etc, we evaluated the influence and mechanism of LMNB1 on LUAD cell line proliferation in vitro and in vivo. Results: According to bioinformatics analysis, LMNB1 is substantially abundant in LUAD tissues and is associated with tumor stage and patient survival (P < 0.05). After silencing LMNB1, the rate of cell growth, wound healing, the number of transwells, and the number of cell colonies all decreased significantly (P < 0.01). With the decreased LMNB1 expression, H3K9me3 protein expression decreases, chromosome accessibility increases, P53, P21, P16 and γ-H2AX protein expression increases, and the number of senescence staining positive cells increases. At the same time, in vivo mouse xenograft experiments showed that the tumor volume of the LMNB1-silenced group was significantly reduced, compared to that of the control group (P < 0.01), and the proliferation biomarker Ki-67 level (P < 0.01) was considerably reduced. Conclusions: Overexpression of LMNB1 in LUAD cells is significant, which has excellent potential to be an indicator for evaluating the clinical prognosis of LUAD patients and a target for precise treatment.

Prevalence and genotype distribution of human papillomavirus infection among women aged 30-65 years in Xi'an, China: a population-based study of 14,655 women.

Cervical cancer is the fourth most common cancer among women worldwide in terms of both incidence and mortality. Persistent infection with high-risk human papillomavirus (HPV) has been identified as a cause of cervical intraepithelial neoplasia and invasive cervical cancer. The distribution of human papillomavirus genotypes varies regionally. To acquire baseline data on the population-based prevalence and genotype distribution of HPV infection, we investigated the molecular epidemiology of HPV infection among women in Xi'an, China. The study was conducted from September 2018 to December 2020. A total of 14,655 women aged 30-65 years were screened. The overall prevalence of HPV infection was 13.5% (95% confidence interval [CI]: 13.0-14.1%), with 10.4% of participants being positive for a single HPV type and 3.1% being positive for multiple HPV types. The prevalence of high-risk HPV (HR-HPV), low-risk HPV (LR-HPV) and mixed HPV infection was 10.1% (95% CI: 9.6-10.5%), 2.2% (95% CI: 2.0-2.4%), and 1.3% (95% CI: 1.1-1.5%), respectively. The five most frequently detected HR-HPV types were types 52 (2.6%), 16 (1.9%), 53 (1.8%), 58 (1.4%), and 51 (0.9%). The most frequently detected LR-HPV type was HPV-42 (1.1%). The prevalence and HPV genotype distribution varied by region and age. Age-specific HPV prevalence peaked in the over 60 years age group (18.8%), and Beilin District had the highest HPV prevalence (18.1%). The results of this first population-based study provide a reference for HPV-based cervical cancer screening and HPV vaccination programs in Xi'an.

Capsid destabilization and epitope alterations of human papillomavirus 18 in the presence of thimerosal.

Thimerosal has been widely used as a preservative in drug and vaccine products for decades. Due to the strong propensity to modify thiols in proteins, conformational changes could occur due to covalent bond formation between ethylmercury (a degradant of thimerosal) and thiols. Such a conformational change could lead to partial or even complete loss of desirable protein function. This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus (HPV) 18 virus-like particles (VLPs). Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed. Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration. Two highly neutralizing antibodies, 13H12 and 3C3, were found to be the most sensitive to thimerosal treatment. The kinetics of antigenicity loss, when monitored with 13H12 or 3C3 as probes, yielded two distinctly different sets of kinetic parameters, while the data from both monoclonal antibodies (mAbs) followed a biphasic exponential decay model. The potential effect of thimerosal on protein function, particularly for thiol-containing proteinaceous active components, needs to be comprehensively characterized during formulation development when a preservative is necessary.

MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling.

BACKGROUND: Histone epigenetic modification disorder is an important predisposing factor for the occurrence and development of many cancers, including colorectal cancer (CRC). The role of MYSM1, a metalloprotease that deubiquitinates monoubiquitinated histone H2A, in colorectal cancer was identified to evaluate its potential clinical application value. METHODS: MYSM1 expression levels in CRC cell lines and tumor tissues were detected, and their associations with patient survival rate and clinical stage were analyzed using databases and tissue microarrays. Gain- and loss-of-function studies were performed to identify the roles of MYSM1 in CRC cell proliferation, apoptosis, cell cycle progression, epithelial-mesenchymal transition (EMT) and metastasis in vitro and in vivo. ChIP, rescue assays and signal pathway verification were conducted for mechanistic study. Immunohistochemistry (IHC) was used to further assess the relationship of MYSM1 with CRC diagnosis and prognosis. RESULTS: MYSM1 was significantly downregulated and was related to the overall survival (OS) of CRC patients. MYSM1 served as a CRC suppressor by inducing apoptosis and inhibiting cell proliferation, EMT, tumorigenic potential and metastasis. Mechanistically, MYSM1 directly bound to the promoter region of miR-200/CDH1, impaired the enrichment of repressive H2AK119ub1 modification and epigenetically enhanced miR-200/CDH1 expression. Testing of paired CRC patient samples confirmed the positive regulatory relationship between MYSM1 and miR-200/CDH1. Furthermore, silencing MYSM1 stimulated PI3K/AKT signaling and promoted EMT in CRC cells. More importantly, a positive association existed between MYSM1 expression and a favorable CRC prognosis. CONCLUSIONS: MYSM1 plays essential suppressive roles in CRC tumorigenesis and is a potential target for reducing CRC progression and distant metastasis.

Pegfilgrastim safety and efficacy on the last chemotherapy day versus the next: systematic review and meta-analysis.

OBJECTIVES: To investigate the efficacy and safety of pegfilgrastim administered on the day of chemotherapy completion (same day) versus at least 1 day after chemotherapy (next day). METHODS: We searched relevant literature published before April 2020 from the following databases: Embase, PubMed, Cochrane databases and Web of science. RESULTS: One randomised controlled trial and 12 observational studies met all of the prespecified criteria for eligibility. The meta-analysis showed a significantly higher febrile neutropenia (FN) rate for the same-day group than that for the next-day arm in the first chemotherapy cycle (OR=2.56, 95% CI 1.19 to 5.48, p=0.02), and in all chemotherapy cycles (OR=1.54, 95% CI 1.29 to 1.84, p<0.00001). Results of subgroup analysis showed a higher FN rate in the same-day arm than in the next-day group for patients with breast cancer (OR=5.50, 95% CI 2.29 to 13.23, p=0.0001) and lymphoma (OR=1.53, 95% CI 1.00 to 2.34, p=0.05). The pooled analysis of studies on gynaecological malignancies showed that patients in the same-day group had a higher incidence of bone pain (OR=1.30, 95% CI 1.01 to 1.68, p=0.04) and a lower incidence of chemotherapy delay (OR=0.71, 95% CI 0.53 to 0.96, p=0.03) compared with the next-day group. CONCLUSIONS: Same-day administration of pegfilgrastim resulted in increased incidence of FN compared with the next-day schedule. This is especially true for patients with breast cancer or lymphoma. These results do not support same-day administration of pegfilgrastim .

High-performance MoOx/n-Si heterojunction NIR photodetector with aluminum oxide as a tunneling passivation interlayer.

The most effective and potential approach to improve the performance of heterojunction photodetectors is to obtain favorable interfacial passivation by adding an insertion layer. In this paper, MoOx/Al2O3/n-Si heterojunction photodetectors with excellent photocurrents, responsivity and detectivity were fabricated, in which alumina acts as a tunneling passivation layer. By optimizing the post-annealing treatment temperature of the MoOxand the thickness of the ultra-thin Al2O3, the photodetector achieved a ratio of photocurrent to dark current of 3.1 × 105, a photoresponsivity of 7.11 A W-1(@980 nm) and a detective of 9.85 × 1012Jones at -5 V bias. Besides, a self-driven response of 0.17 A W-1and a high photocurrent/dark current ratio of 2.07 × 104were obtained. The result demonstrated that optimizing the interface of heterojunctions is a promising way to obtain a heterojunction photodetector with high-performance.

A new 7-gene survival score assay for pancreatic cancer patient prognosis prediction.

Gene expression features that are valuable for pancreatic ductal adenocarcinoma (PDAC) prognosis are still largely unknown. We aimed to explore pivotal molecular signatures for PDAC progression and establish an efficient survival score to predict PDAC prognosis. Overall, 163 overlapping genes were identified from three statistical methods, including differentially expressed genes (DEGs), coexpression network analysis (WGCNA), and target genes for miRNAs that were significantly related to PDAC patients' overall survival (OS). Then, according to the optimal value of the cross-validation curve (lambda = 0.031), 7 non-zero coefficients (ARNTL2, DSG3, PTPRR, ANLN, S100A14, ANKRD22, and TSPAN7) were selected to establish a prognostic prediction model of PDAC patients. We further confirmed the expression level of 7 genes using RT-PCR, western blot, and immunohistochemistry staining in PDAC patients' tissues. Our results showed that the ROC curve of the 7-mRNA model indicated good predictive ability for 1- and 2-year OS in three datasets (TCGA: 0.71, 0.69; ICGC: 0.8, 0.74; GEO batch: 0.61, 0.7, respectively). The hazard ratio (HR) of the low-risk group had a similar significant result (TCGA: HR = 0.3723; ICGC: HR = 0.2813; GEO batch: HR = 0.4999; all P < 0.001). Furthermore, Log-rank test results in three cohorts showed that the 7-mRNA assay excellently predicted the prognosis and metastasis, especially in TNM stage I&II subgroups of PDAC. In conclusion, the strong validation of our 7-mRNA signature indicates the promising effectiveness of its clinical application, especially in patients with TNM stages I&II.

S100A16 induces epithelial-mesenchymal transition in human PDAC cells and is a new therapeutic target for pancreatic cancer treatment that synergizes with gemcitabine.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a poor 5-year survival rate of approximately 6%, mostly due to poor treatment response and early progression. The S100 gene family participates in various pathophysiological processes in various malignancies. S100A16 is a member of the S100 family, which is abnormally expressed in PDAC; however, its biological functions and mechanisms of action remain unclear. We analysed the Gene Expression Omnibus (GEO) public database and the gene ChIP data collected in our previous study of human PDAC cell line PANC-1 cocultured with M2 macrophages to identify differentially expressed genes (DEGs). Twenty-three overexpressed genes were identified by screening. Then, the selected genes were analysed using The Cancer Genome Atlas (TCGA) database to assess whether they have significant impact on the overall survival (OS) of PDAC patients. Of the 14 DEGs identified, S100A16 was associated with poor prognosis and was selected for further investigation; the results indicate that S100A16 is positively correlated with epithelial-mesenchymal transition (EMT)-related genes in the TCGA dataset. Subsequent in vitro and in vivo experiments demonstrated that S100A16 induces the EMT to promote the metastasis of human PDAC cells and that the effect is mediated by the enhanced expression of TWIST1 and activation of the STAT3 signalling pathway. The antitumour effect of gemcitabine (GEM) was enhanced in combination with S100A16 downregulation. In conclusion, our findings suggest that S100A16 is a novel potential therapeutic target for human PDAC treatment.

miR­193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma.

Emerging evidence has indicated that microRNAs (miRs) are involved in the malignant behavior of cancer. The present study explored the role of miR­193b in the development and metastasis of osteosarcoma. Compared with F4 osteosarcoma cells, which have a relatively low metastatic potential, highly metastatic F5M2 cells exhibited a lower expression of miR­193b. Furthermore, miR­193b exerted negative effects on cell proliferation, colony formation, cell cycle progression, migration and invasion, and induced apoptosis. In vivo studies revealed negative influences of miR­193b on tumorigenesis and metastasis. The tumor­suppressive role of miR­193b was achieved by targeting KRAS and stathmin 1 (STMN1). Notably, overexpression of KRAS and STMN1 attenuated the miR­193b­induced inhibition of malignant behaviors. There was a double­negative regulatory loop between MYC and miR­193b, with MYC inhibiting miR­193b expression by directly binding to its promoter region and miR­193b negatively influencing MYC expression indirectly through some unknown mechanism. Collectively, these findings indicated that miR­193b may serve a tumor suppressive role in osteosarcoma by targeting KRAS and STMN1. The double­negative regulatory loop between MYC and miR­193b may contribute to the sustained upregulation of MYC, the downregulation of miR­193b, and to the subsequently enhanced expression of KRAS and STMN1, which may eventually lead to the development and metastasis of osteosarcoma.

Effects of serratus anterior plane block for postoperative analgesia after thoracoscopic surgery compared with local anesthetic infiltration: a randomized clinical trial.

BACKGROUND: Serratus anterior plane (SAP) block is a relatively novel technique that can block the lateral cutaneous branches of the intercostal nerves as well as the long thoracic nerve. PURPOSE: Our study aimed to evaluate the effects of SAP block on postoperative pain after thoracoscopic surgery compared with local anesthetic (LA) infiltration. PATIENTS AND METHODS: Forty adult patients undergoing video-assisted thoracic surgery were randomized to receive either SAP block (n=20) or LA infiltration of incision (n=20). The primary outcome was postoperative visual analog scale (VAS) score at the 2nd, 8th, 16th, 24th, and 48th hour after surgery. The secondary outcomes were the consumption of sufentanil at 8th, 16th, 24th hours postoperative. In addition, rescue analgesia, drug-related adverse effects after surgery was also analyzed. RESULTS: The SAP group showed lower VAS scores at the 2nd hour (at rest: SAP group 11 [8-13] vs LA group 28 [26-32], P=0.01; on coughing: 15 [13-18] vs 33 [26-38], P=0.01) and the 8th hour (at rest: 13 [12-18] vs 36 [32-46], P=0.01; on coughing: 19 [16-23] vs 42 [36-53], P=0.01) after surgery. Postoperative sufentanil consumption in the SAP group during 0-8 hrs was significantly lower compared with the LA group (P<0.01). The use of rescue analgesia was also significantly lower in the SAP group (P=0.02) during 0-12 hrs. CONCLUSION: Compared to LA infiltration, ultrasound-guided SAP block may provide better pain relief as well as reduce opioid consumption after thoracoscopic surgery.

Multiple "Omics" data-based biomarker screening for hepatocellular carcinoma diagnosis.

The huge prognostic difference between early and late stage hepatocellular carcinoma (HCC) is a challenging diagnostic problem. Alpha-fetoprotein is the mostly widely used biomarker for HCC used in the clinic, however it's sensitivity and specificity of is not optimal. The development and application of multiple biotechnologies, including next generation sequencing, multiple "omics" data, that include genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics has been used for HCC diagnostic biomarker screening. Effective biomarkers/panels/models have been identified and validated at different clinical levels. A large proportion of these have a good diagnostic performance for HCC, especially for early HCC. In this article, we reviewed the various HCC biomarkers derived from "omics" data and discussed the advantages and disadvantages for diagnosis HCC.

MiR-9 promotes tumorigenesis and angiogenesis and is activated by MYC and OCT4 in human glioma.

BACKGROUND: Glioma, characterized by its undesirable prognosis and poor survival rate, is a serious threat to human health and lives. MicroRNA-9 (miR-9) is implicated in the regulation of multiple tumors, while the mechanisms underlying its aberrant expression and functional alterations in human glioma are still controversial. METHODS: Expressions of miR-9 were measured in GEO database, patient specimens and glioma cell lines. Gain- and loss-of-function assays were applied to identify the effects of miR-9 on glioma cells and HUVECs in vitro and in vivo. Potential targets of miR-9 were predicted by bioinformatics and further verified via in vitro experiments. Transcriptional regulation of miR-9 by MYC and OCT4 was determined in glioma cells. RESULTS: MiR-9 was frequently up-regulated in glioma specimens and cells, and could significantly enhance proliferation, migration and invasion of glioma cells. In addition, miR-9 could be secreted from glioma cells via exosomes and was then absorbed by vascular endothelial cells, leading to an increase in angiogenesis. COL18A1, THBS2, PTCH1 and PHD3 were verified as the direct targets of miR-9, which could elucidate the miR-9-induced malignant phenotypes in glioma cells. MYC and OCT4 were able to bind to the promoter region of miR-9 to trigger its transcription. CONCLUSIONS: Our results highlight that miR-9 is pivotal for glioma pathogenesis and can be treated as a potential therapeutic target for glioma.